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C Morton

Publications and source records attributed to C Morton.

At least 19 recordsLinked to original sources
PubMed1999

A case-control study of melanomas of the soles and palms (Australia and Scotland).

OBJECTIVES: Because the factors that influence risk of acral melanomas on the soles and palms in White populations are unknown, we investigated these in a multi-center case-control study. METHODS: Cases of melanoma of the feet and hands diagnosed from 1987-93 in persons aged over 18 years were ascertained in eastern Australia and western Scotland. There were 275 cases of melanoma on the soles and palms matched to 496 controls (selected from the electoral roll) in Australia, and 36 cases matched to 72 controls (nominated by general practitioners) in Scotland. RESULTS: Acral melanoma was strongly associated with high total body nevus counts (adjusted relative risk [RR] = 6.3, 95% confidence interval [CI] = 2.5-15.6), and with nevi on the soles (RR = 7.5, CI = 3.0-18.6). There were also significant positive associations with a penetrative injury of the feet or hands (RR = 5.0, CI = 3.0-8.6) and with heavy exposure to agricultural chemicals (RR = 3.6, CI = 1.5-8.3). Sun-sensitive complexions, cumulative sun exposure and a past history of nonmelanoma skin cancer were also associated with increased risk of acral melanoma. Current cigarette smoking was inversely related to acral melanoma (RR = 0.6, CI = 0.4-0.9). CONCLUSIONS: Melanomas of the soles and palms resemble other cutaneous melanomas in their association with sun exposure, but are distinguished from them by their strong positive associations with nevi on the soles, previous penetrative injury, and exposure to agricultural chemicals, and by their inverse association with smoking.

Adolescent↗
PubMed1997

Structure and chromosomal assignment of the human cathepsin K gene.

Cathepsin K is a recently identified lysosomal cysteine proteinase that is the major protease responsible for bone resorption and remodeling. Mutations in this gene cause the sclerosing osteochondrodysplasia pycnodysostosis. To assess its evolutionary relatedness to other cysteine proteases and to facilitate mutation identification in patients with pycnodysostosis, a genomic clone, 74e16, containing the cathepsin K gene was isolated from a human PAC library, and the cathepsin K genomic structure was determined. The cathepsin K gene contained eight exons and spanned approximately 9 kb. The transcription initiation site, determined by primer extension analysis, was 169 nucleotides upstream from the translation initiation site. The 5'-flanking region lacked a TATA box but contained two AP1 sites. Comparison of genomic and cDNA sequences suggested that this flanking sequence may be the major promoter in osteoclasts and macrophages. Cathepsin K was mapped to chromosome 1q21 by fluorescence in situ hybridization and found to reside within 150 kb of an evolutionarily related cysteine protease, cathepsin S. These findings expand our understanding of the papain family lysosomal cysteine proteases and should facilitate mutation analysis in pycnodysostosis.

Base Sequence↗
PubMed1996

Stimulated mitogen-activated protein kinase is necessary but not sufficient for the mitogenic response to angiotensin II. A role for phospholipase D.

Activation of the mitogen-activated protein kinase (MAPK) cascade has been widely associated with cell proliferation; previous studies have shown that angiotensin II (AII), acting on 7-transmembrane G protein-coupled receptors, stimulates the MAPK pathway. In this report we investigate whether the MAPK pathway is required for the mitogenic response to AII stimulation of vascular smooth muscle cells derived from the hypertensive rat (SHR-VSM). AII stimulates the phosphorylation of MAPK, as determined by Western blot specific for the tyrosine 204 phosphorylated form of the protein. This MAPK phosphorylation was inhibited by the presence of the inhibitor of MAPK kinase activation, PD 098059. Using a peptide kinase assay shown to measure the p42 and p44 isoforms of MAPK, the stimulated response to AII was inhibited by PD 098059 with an IC50 of 15.6 +/- 1.6 microM. The AII stimulation of [3H]thymidine incorporation was inhibited by PD 098059 with an IC50 of 17.8 +/- 3.1 microM. PD 098059 had no effect on AII-stimulated phospholipase C or phospholipase D (PLD) activity. When the SHR-VSM cells were stimulated with phorbol ester, there was an activation of MAPK similar in size and duration to the response to AII, but there was no significant enhancement of [3H]thymidine incorporation. There was also no activation of PLD by phorbol ester, while AII produced a robust PLD response. Diversion of the product of the PLD reaction by 1-butanol caused a partial loss of the [3H]thymidine response; this did not occur with tertiary butanol, which did not interfere with the PLD reaction. These results show that in these cells the MAPK cascade is required but not sufficient for the mitogenic response to AII, and suggest that the full mitogenic response requires both MAPK in conjunction with other signaling components, one of which is PLD.

Angiotensin II↗
PubMed1996

Systemic effects of screening for retinopathy of prematurity.

AIMS: To detect systemic complications of screening for retinopathy of prematurity (ROP), paying particular attention to the physical examination. METHODS: Oxygen saturation, pulse rate, and blood pressure were monitored before, during, and after 110 ROP screening examinations. RESULTS: Following topical mydriatics diastolic blood pressure was elevated by a mean of 6 (SD 7.2) mm Hg. Immediately after the examination there was a further rise in both systolic and diastolic pressure of 4.3 (14.5) mm Hg and 3.3 (11.6) mm Hg, respectively. Oxygen saturation and pulse rate remained stable during the control period and administration of eyedrops. Saturation fell by a median of 3% (95% confidence interval plus or minus 1.2%) after the examination while there was rise in pulse rate of 7 (SD 23.1) beats per minute. This change in pulse rate was not observed in infants on concurrent methylxanthine therapy. No infant had clinically significant changes at the end of the study. CONCLUSION: The initial changes in blood pressure may represent side effects of topical mydriatics but the later changes following the physical examination may be an additional response to the stress of ROP screening.

Anesthetics, Local↗
PubMed1995

Effects of nitrous oxide on psychological performance. A dose-response study using inhalation of concentrations up to 15%.

In this six-period randomised double-blind study, 12 healthy volunteers inhaled mixtures of nitrous oxide at concentrations of 0% (placebo); 3%, 5%, 7%, 10%, and 15% in oxygen. Each concentration was inhaled for 55 min, each period being on a separate day. The order of treatments was randomised using a Latin-Square design. The effects of nitrous oxide were assessed using a battery of performance tests which included measures of attention, psychomotor function, memory and cognition. Mood was assessed using visual analogue scales. Measures of attention and psychomotor performance showed impairment at 15% nitrous oxide, and subjective measures showed sedation at this dose. The Buschke Selective Reminding Task showed impairment to long-term recall at all doses of nitrous oxide compared to placebo, while short-term recall was impaired only at 15%. These results suggest that consolidation of memory may be particularly sensitive to disruption as a result of CNS depression.

Administration, Inhalation↗
PubMed1995

Stimulation of two vascular smooth muscle-derived cell lines by angiotensin II: differential second messenger responses leading to mitogenesis.

1. We show here that angiotensin II (AII) and endothelin-1 (ET-1) stimulate [3H]-thymidine incorporation in a smooth muscle cell line derived from aortae of spontaneously hypertensive rats (SHR), but not in cells derived from normotensive controls (WKY). We have used the differential response of the two cell lines to investigate the relationship between second messenger systems and the mitogenic response. 2. AII produced an increase in accumulation of inositol 1,4,5-triphosphate which was greater in the SHR-derived cell line than in the WKY cells. 3. AII gave an increase in cytosolic Ca2+ in each of the cell lines, with both a larger peak (15-30 s) and plateau response (2 min) in the SHR cells. ET-1 gave an enhanced response in the SHR-derived cells with respect to the peak but not the plateau of cytosolic Ca2+. 4. Phospholipase D activity was studied by monitoring the formation of [3P]-phosphatidylbutanol in 32Pi prelabelled cells. AII stimulation gave a larger phospholipase D response in the SHR-derived cells, while ET-1 gave a larger response in WKY-derived cells. 5. Stimulation of SHR-derived cells with 100 nM AII for 1 h, followed by 19 h in the absence of agonist, stimulated [3H]-thymidine incorporation over the next 4 h. When the 1 h stimulation with AII was in the presence of increasing concentrations of butanol, which diverts the product of the phospholipase D pathway, there was a loss of stimulated [3H]-thymidine incorporation which was significant at 10 mM butanol and at 30-50 mM reached a maximum loss of 40%. 6. Contrasting with this there was no apparent loss of ET-l-stimulated thymidine incorporation when butanol was present at concentrations up to 40 mM.7. These results suggest that phospholipase D is one of several pathways in the mitogenic response of SHR-derived vascular smooth muscle cells to All.

Angiotensin II↗
PubMed1994

A study of chromium induced allergic contact dermatitis with 54 volunteers: implications for environmental risk assessment.

Over the past 60 years, dose-response patch test studies by various methods have been conducted in an attempt to identify the minimum elicitation threshold (MET) concentration of hexavalent chromium (Cr(VI)) that produces an allergic response in Cr(VI) sensitive subjects. These data are not adequate, however, to provide an accurate estimate of the MET because of the variability in the patch testing techniques and the variability in diagnostic criteria used. Furthermore, the data were not reported in terms of mass of allergen per surface area of skin (mg Cr/cm2-skin), which is necessary for conducting occupational or environmental health risk assessments. Thus the purpose of this study was to determine the MET (mg allergen/cm2) for Cr(VI) and trivalent chromium (Cr(III)) by patch testing techniques. A patch test method that delivers a controlled amount of allergen per surface area of skin was used. A group of 54 Cr(VI) sensitised volunteers were patch tested with serial dilutions of Cr(VI) and Cr(III) to determine the cumulative response rate at several concentrations. The results indicate that the 10% MET for Cr(VI) based on the cumulative response was 0.089 micrograms Cr(VI)/cm2-skin. Only one of the 54 volunteers may have responded to 33 micrograms Cr(III)/cm2-skin, otherwise Cr(III) was unable to produce allergic contact dermatitis in these highly sensitive volunteers. Two supplemental studies were also conducted to assess whether the surface area of the patch and the concentration of Cr(VI) in the patch (related to patch thickness) were likely to influence the results. The data from these studies were used to assess the risk of developing allergic contact dermatitis due to contact with Cr(VI) and Cr(III) in soil. The findings indicated that soil concentrations at least as high as 450 ppm Cr(VI) and 165,000 ppm Cr(III) should not pose an allergic contact dermatitis hazard for at least 99.99% of the people in the community who might be exposed.

Adult↗
PubMed1993

Measurement of cremophor EL following taxol: plasma levels sufficient to reverse drug exclusion mediated by the multidrug-resistant phenotype.

BACKGROUND: Paclitaxel (Taxol) is the first of a new class of cytotoxic agents with activity against tumors resistant to other drugs. For clinical use, paclitaxel is currently formulated in a vehicle of 50% ethanol and 50% polyethoxylated surfactant Cremophor EL (Cremophor). We have previously shown that Cremophor will block the P-glycoprotein drug efflux pump responsible for the multidrug-resistant phenotype. Overexpression of P-glycoprotein is one mechanism of in vitro resistance to a number of currently used cytotoxic agents including paclitaxel. PURPOSE: Our aim was to develop a bioassay to measure plasma levels of Cremophor and to determine whether or not plasma levels of Cremophor achieved during paclitaxel therapy are sufficient to inhibit the activity of the P-glycoprotein. METHODS: All patients studied had histologically proven, advanced ovarian carcinoma with measurable or evaluable disease and had received at least one prior platinum-containing regimen. The bioassay used flow cytometry to measure the increase in equilibrium intracellular daunorubicin levels in multidrug-resistant human T-cell leukemia cells (CEM/VLB100) in the presence of a series of concentrations of Cremophor. Levels of Cremophor were measured in plasma from 21 patients after a 3-hour infusion of 135 or 175 mg/m2 paclitaxel. Both dose levels were given following premedication with oral dexamethasone, intravenous promethazine hydrochloride, and intravenous cimetidine. The Cremophor bioassay involved incubation of CEM/VLB100 cells (5 x 10(5)) for 1 hour with 2 micrograms/mL daunorubicin in 0.5 mL HL-1 medium plus 0.5 mL plasma prior to flow cytometric analysis. Pretreatment plasma was used to derive a standard curve for the effect of Cremophor on equilibrium daunorubicin levels. All measurements were done in triplicate. RESULTS: In vitro experiments indicated that, for maximal inhibition of P-glycoprotein activity, concentrations of Cremophor of 0.1% (vol/vol) were required. At the end of a 3-hour infusion of paclitaxel, plasma levels of Cremophor in 19 of 21 patients were 0.1% or higher and 0.09% in the remaining two. Concentrations of 5-20 microM paclitaxel dissolved in ethanol without Cremophor did not inhibit P-glycoprotein in this assay. CONCLUSION: The concentrations of Cremophor measured in plasma drawn from patients after a 3-hour infusion of paclitaxel at 135 or 175 mg/m2 were found to be sufficient to inhibit P-glycoprotein activity in vitro. IMPLICATIONS: The efficacy of paclitaxel against some tumors may be aided by its administration in a vehicle solution containing Cremophor in quantities that reach concentrations in the plasma sufficient to reverse multidrug resistance of neoplastic cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Dog identification.

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Animal Identification Systems↗
PubMed1991

Comparative semen cryopreservation in ferrets (Mustela putorius furo) and pregnancies after laparoscopic intrauterine insemination with frozen-thawed spermatozoa.

A study was conducted to determine an optimum technique for semen cryopreservation and the biological competence of frozen-thawed ferret spermatozoa. Fifty-two fresh electroejaculates from 4 males were evaluated for sperm percentage motility, forward progressive motility, motility index (SMI) and acrosomal integrity. To determine the optimum temperature for maintaining sperm motility in vitro and the influence of glycerol on sperm motility, seminal aliquants were diluted in TEST diluent (containing either 0 or 4% glycerol) and maintained at 25 degrees or 37 degrees C. For cryopreservation, semen was diluted in each of 3 cryodiluents (TEST, PDV, BF5F), cooled for 30 min at 5 degrees C and pelleted on solid CO2 or frozen in 0.25 ml straws (20 degrees C/min to -100 degrees C). Following thawing, SMI and acrosomal integrity were determined. Ten females with maximum vulval swelling were given 90 i.u. human chorionic gonadotrophin and laparoscopically inseminated in utero with spermatozoa previously frozen using the optimum diluent and freeze-thaw method. The maintenance temperature of 25 degrees C was superior (P less than 0.05) to 37 degrees C for sustaining sperm motility, and glycerol did not influence (P greater than 0.05) motility for up to 11 h of culture. After thawing, motile spermatozoa were recovered in all treatment groups, but sperm motility and normal acrosomal ratings were highest using the PDV diluent, the pelleting method and thawing at 37 degrees C (P less than 0.05). Seven of the 10 ferrets (70%) inseminated with spermatozoa frozen by this approach became pregnant and produced 31 kits (mean litter size 4.4; range 1-9 kits).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Birth of the first 100 babies in Hawaii after conception in-vitro: experience at the Pacific In-Vitro Fertilization Institute.

This paper reports on the first 100 infants delivered consecutively the result of 63 pregnancies after conception in-vitro at the Pacific In-Vitro Fertilization (IVF) Institute. These pregnancies were established prior to the introduction of embryo-cryopreservation into the program. Ninety-seven percent (97%) of singleton pregnancies delivered after 36 weeks; only 5/31 (16%) required tocolytic therapy. The overall multiple gestation rate was 51%, higher than in many other IVF centers. Maternal complications and neonatal morbidity were associated primarily with these multiple gestations. Forty-one percent (41%) delivered in less than 36 weeks, and tocolytics were administered in 22/27 (81%) of twin and 5/5 (100%) of triplet gestations. Neonatal morbidity was noted in 39 infants (33 from multiple gestations); 28 neonates were admitted to the intensive care unit (27 from multiple gestations). Nine births had or developed minor abnormalities (hernias, pyloric stenosis). One case of Trisomy 21, and one infant death at 11 months occurred in the group. The caesarean section rate for all IVF deliveries was 65%. It is concluded that IVF is clearly established in Hawaii for infertility refractory to other methods of treatment. The risk associated with IVF stem from the possibility of multiple gestations, not whether the pregnancy was initiated in-vitro. In the future, embryo cryopreservation may help to reduce the risk of multiple pregnancy.

Adult↗
PubMed1990

Complete amino acid sequence of tenebrosin-C, a cardiac stimulatory and haemolytic protein from the sea anemone Actinia tenebrosa.

The complete amino acid sequence of the cardiac stimulatory and haemolytic protein tenebrosin-C, from the Australian sea anemone Actinia tenebrosa, has been determined by Edman degradation of the intact molecule and fragments produced by treatment of the polypeptide chain with cyanogen bromide and enzymatic cleavage with endoproteinase Asp-N, thermolysin and trypsin. The molecule is a single-chain polypeptide consisting of 179 amino acid residues with a calculated molecular mass of 19,797 Da. Tenebrosin-C shows a high degree of amino acid sequence similarity (63%) with Stoichactis helianthus cytolysin III [Blumenthal, K. M. and Kem, W. R. (1983) J. Biol. Chem. 258, 5574-5581] and is identical to a partial sequence (90 residues) reported for equinatoxin, a cardiostimulatory and haemolytic protein isolated from the European sea anemone Actinia equina [Ferlan, I. and Jackson, K. (1983) Toxicon Suppl. 3, 141-144]. No amino acid sequence similarity was detected between tenebrosin-C and other protein sequences stored in available databases. The predicted secondary structure of tenebrosin-C suggests that it is a compact, highly structured molecule.

Amino Acid Sequence↗