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R Chapman

Publications and source records attributed to R Chapman.

At least 37 records · Page 2Linked to original sources
PubMed2000

Mass spectral fragmentation pathways in cyclic difluoramino and nitro compounds

The recently synthesized compounds 4, 4-bis(difluoramino)-1-nitropiperidine (I), 1,4,4-trinitropiperidine (II), 1,1,4,4-tetranitrocyclohexane (III), 1,1,4, 4-tetrakis(difluoramino)cyclohexane (IV) and 3,3,7, 7-tetrakis(difluora-mino)octahydro-1,5-dinitro-1,5-diazocine (HNFX, V) are being considered as potential energetic materials. The mass spectra of these compounds were studied using electron ionization (EI) mass spectrometry. A collision-induced dissociation (CID) study of the major EI peaks was carried out using a Finnigan TSQ 700 tandem mass spectrometer. The mass fragmentation pathways are constructed and discussed. The decomposition of HNFX (V), under EI, appeared to parallel the thermal decomposition of nitramines where N-NO(2) cleavage is often the first step. However, the two nitramines with a six-membered ring structure (I and II) underwent initial loss of a geminal substituent; loss of a nitramine nitro group was the secondary step. The two cyclohexane structures (III and IV) showed similar initial fragmentation pathways, featuring successive losses of nitro or difluoramino groups. Copyright 2000 John Wiley & Sons, Ltd.

Journal Article↗
PubMed2000

Multiple factors other than p53 influence colon cancer sensitivity to paclitaxel.

PURPOSE: To determine factors which influence the sensitivity of human colorectal carcinoma cell lines to paclitaxel. METHODS: The paclitaxel sensitivity of ten human colorectal carcinoma cell lines, and a panel of RKO colon carcinoma cell lines, isogenic except for p53 status, were studied. The inhibitory concentrations causing a 50% decrease in growth (IC50) were assayed after 3, 24, and 96 h after paclitaxel exposure. The doubling time (DT) and cell cycle parameters of cells were also measured. The expression of the multidrug resistance glycoprotein-1 (MDR-1), bcl-2 and bax was quantitatively assessed by immunoblotting. RESULTS: Mean IC50 values at 24 and 96 h drug exposure were about 1.5 logs lower than the IC50 values at 3 h, regardless of the p53 status. No difference was found between the IC50 values of wild-type and mutant p53 cells, or among the RKO panel of cells. Correlation analysis showed that: (1) resistance was associated with longer DTs, but this was generally abated by a 96-h exposure; (2) with a 3-h exposure, the combination of MDR, bcl-2 and bax parameters with DT (DT + MDR + bcl-2 bax) best correlated with IC50 values (r = 0.77); (3) with a 96-h exposure, in spite of the generally decreased IC50 values, a combination of MDR-1, bcl-2 and bax parameters (MDR + bcl-2-bax) best correlated with the IC50 values (r = 0.71). CONCLUSIONS: These results suggest that the exposure duration, DT, and expression of MDR-1, bcl-2 and bax each contribute to paclitaxel sensitivity of human colorectal carcinoma cells. In assessing paclitaxel drug resistance, multiple factors should always be considered. There may be a therapeutic window for taxanes in colon cancer by optimizing pharmacokinetics and modulating MDR-1 and bcl-2 resistance factors.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Procathepsin L self-association as a mechanism for selective secretion.

The lysosomal cysteine pro-protease procathepsin L was enriched in dense vesicles detectable when microsomes prepared from wild-type or transformed mouse fibroblasts were resolved on sucrose gradients. These dense vesicles did not comigrate with proteins characteristic of the endoplasmic reticulum, Golgi, endosomes or lysosomes. When gradient fraction vesicles were lysed at acidic pH in the presence of excess mannose 6-phosphate to prevent binding to mannose phosphate receptors, the majority of the procathepsin L was associated with the membrane, not the soluble, fraction. Immunogold labeling of procathepsin L in thin sections of cells or gradient fractions, using antibodies directed against the propeptide to avoid detection of the mature enzyme in dense lysosomes, revealed that the proenzyme was concentrated in dense cores localized in small vesicles near the plasma membrane and in multivesicular bodies. Consistent with the density of the gradient fraction and the electron density of the cores, yeast two-hybrid assays indicated the proenzyme could bind itself but could not interact with the aspartic proprotease procathepsin D. The data suggest that in mouse fibroblasts procathepsin L may self-associate into aggregates, initiating the formation of dense vesicles that could mediate the selective secretion of procathepsin L independent of mannose phosphate receptors.

Animals↗
PubMed2000

Digit span in individuals with Down syndrome and in typically developing children: temporal aspects.

This study explored factors influencing digit span performance in individuals with Down syndrome. The following questions were asked: Is there a deficit in the phonological loop, either in articulatory rehearsal (measured in speaking rate and recall latency) or in the passive store (measured in recall duration)? Is reduced auditory short-term memory associated with a language production deficit? Thirty five adolescents with trisomy 21 Down syndrome were compared to 35 mental-age-matched and 35 language-production-matched controls. There was no group difference in speaking rate. The DS group had shorter digit spans than the MA controls. Language production level accounted for substantial variance in digit span in individuals with Down syndrome.

Adolescent↗
PubMed2000

Beam profile measurements and simulations for ultrasonic transducers operating in air

This paper outlines a method that has been implemented to predict and measure the acoustic radiation generated by ultrasonic transducers operating into air in continuous wave mode. Commencing with both arbitrary surface displacement data and radiating aperture, the transmitted pressure beam profile is obtained and includes simulation of propagation channel attenuation and where necessary, the directional response of any ultrasonic receiver. The surface displacement data may be derived directly, from laser measurement of the vibrating surface, or indirectly, from finite element modeling of the transducer configuration. To validate the approach and to provide experimental measurement of transducer beam profiles, a vibration-free, draft-proof scanning system that has been installed within an environmentally controlled laboratory is described. A comparison of experimental and simulated results for piezoelectric composite, piezoelectric polymer, and electrostatic transducers is then presented to demonstrate some quite different airborne ultrasonic beam-profile characteristics. Good agreement between theory and experiment is obtained. The results are compared with those expected from a classical aperture diffraction approach and the reasons for any significant differences are explained.

Journal Article↗
PubMed1999

Activation of nuclear factor kappaB in single living cells. Dependence of nuclear translocation and anti-apoptotic function on EGFPRELA concentration.

We have studied the dynamics of nuclear translocation during nuclear factor kappaB activation by using a p65(RELA)-enhanced green fluorescent protein (EGFP) fusion construct. Quantitation of expression levels indicates that EGFPRELA can be detected at physiological concentrations of about 60,000 molecules per cell. Stimulation of transfected fibroblasts with interleukin (IL)-1beta caused nuclear translocation of EGFPRELA, typically resulting in a 30-fold increase in nuclear protein at maximum induction and a concomitant 20% decrease in cytoplasmic levels. The response of individual cells to IL-1beta was graded, and the kinetics of nuclear translocation were dependent on the dose of IL-1beta and the level of EGFPRELA expression. The rate of nuclear uptake was saturable, and the time lag for uptake increased at higher EGFPRELA expression levels. Furthermore, nuclear translocation was reduced at less than saturating doses of IL-1beta suggesting that the pathway is limited by incoming signals. The response to IL-1beta was biphasic, demonstrating a decline in nuclear import rate at expression levels above three to four times endogenous. This correlated with the anti-apoptotic function of EGFPRELA which was more prominent at low expression levels and demonstrated successively less protection at higher levels. In comparison, transfection of p50 had no effect on the level of apoptosis and demonstrated some toxicity in combination with EGFPRELA.

Apoptosis↗
PubMed1999

Case-control study of mesothelioma in South Africa.

BACKGROUND: South Africa has, uniquely, mined, transported, and used crocidolite, amosite, and chrysotile. A multicenter case-control study was done in South Africa to examine the details of asbestos exposure in cases and controls, and to calculate relative risks for level of certainty of asbestos exposure, nature of exposure (e.g., environmental, occupational) and fiber type. METHODS: Cases and controls (one cancer and one medical per case) were collected by six study centers from referral hospitals, and exposure information was collected by interviewing cases and controls in life. RESULTS: One hundred and twenty-three cases were accepted into the study. None had purely chrysotile exposure. Twenty-three cases had mined Cape crocidolite; three had mined amosite; and three Transvaal crocidolite plus amosite. A minimum of 22 of the cases had exclusively environmental exposure, 20 were from the NW Cape crocidolite mining area. The relative risks associated with environmental exposure in the NW Cape (crocidolite) were larger than for environmental exposure in the NE Transvaal (amosite and crocidolite): 21.9 vs. 7.1 and 50.9 vs. 12.0 for the cancer control and medical control datasets, respectively. CONCLUSIONS: The results confirm the importance of environmental exposure in the Cape crocidolite mining area, the relative paucity of cases linked to amosite, the rarity of chrysotile cases and are consistent with a fiber gradient in mesotheliomagenic potential for South African asbestos with crocidolite > amosite > chrysotile.

Asbestos↗
PubMed1999

Purification and characterization of extracellular lipases from Ophiostoma piliferum.

Interest in lipases from microorganisms, animals, and plants has greatly increased in the past decade due to their applications in biotransformations and organic syntheses. We are reporting the purification and characterization of two lipases from the fungus, Ophiostoma piliferum, a saprophytic organism commonly found on wood. A major and a minor lipase have been co-purified by hydrophobic interaction chromatography on octyl sepharose FF, followed by ion exchange chromatography on Q sepharose FF. The lipases bound very tightly to octyl sepharose resulting in greater than 100-fold purification in this one step. The major lipase has a molecular weight of approximately 60 kDa, a pI of 3.79, and is glycosylated as determined by PAS staining. The minor lipase, which composes 10% of the total protein, has a pI of 3.6, and molecular weight of approximately 52 kDa and did not stain with the PAS reagent. Deglycosylation of the major lipase produced two proteins of lower molecular weight, a 55 kDa protein and a 52 kDa protein. The deglycosylated protein at 52 kDa co-migrates with the minor lipase on SDS-PAGE gels. N-terminal amino acid sequencing of the major and minor lipases indicated both lipases have the same N-termini and MALDI-TOF mass spectral analysis showed similar peptide patterns. Available data indicate that the lipases are derived from the same protein and appear to differ in their post-translational modification as evidenced by their pIs and molecular weight difference. The pH rate profile and thermal stability were determined for the purified O. piliferum lipase and were consistent with a mesophilic lipase. In aqueous solution, the lipases exhibited a higher rate of hydrolysis for p-nitrophenylbutyrate (C4) than for p-nitrophenylstearate (C18), which is an unexpected result.

Amino Acid Sequence↗
PubMed1999

HLA class II haplotypes in primary sclerosing cholangitis patients from five European populations.

The association of primary sclerosing cholangitis (PSC) to HLA class II genes was studied by comparing patients from five different European populations. Deduced HLA-DRB1, DQA1, DQB1 haplotypes of 256 PSC patients from England, Italy, Norway, Spain and Sweden were compared to those observed in 764 ethnically-matched controls. Increased frequencies of the DRB1*03, DQA1*0501, DQB1*02 (RR=3.0, P<0.00001) and the DRB1*13, DQA1*0103, DQB1*0603 haplotypes (RR=2.4, P<0.0001) were observed in all five patient groups. A total of 16% of the PSC patients were homozygous for the DRB1*03, DQA1*0501, DQB1*02 haplotype compared to 1% of the controls (RR=20, P<0.0001). The DRB1*04, DQA1*03, DQB1*0302 haplotype was significantly reduced in frequency(RR=0.4, P<0.00001). Among Norwegian, Swedish and British patients that did not carry neither the DRB1*03, DQA1*0501, DQB1*02 nor the DRB1*13, DQA1*0103, DQB1*0603 haplotype, an increased frequency of the DRB1*15, DQA1*0102, DQB1*0602 haplotype was observed (RR=2.0, P<0.0001). Thus, PSC was found to be positively associated to three different HLA class II haplotypes (i.e. the DRB1*03, DQA1*0501, DQB1*02, the DRB1*15, DQA1*0102, DQB1*0602 and the DRB1*13, DQA1*0103, DQB1*0603 haplotypes) and negatively associated to one HLA class II haplotype (i.e. the DRB1*04, DQB1*0302 haplotype).

Adolescent↗
PubMed1999

Asbestos exposure and mesothelioma in South Africa.

OBJECTIVES: To describe the exposure experiences of South African mesothelioma cases, with emphasis on the contribution made to the caseload by different fibre types, the proportion of subjects with no recall of asbestos exposure and only environmental contact, and the importance of putative causes other than asbestos. DESIGN: A multi-centred case-control study. SUBJECTS AND SETTING: 123 patients with mesothelioma interviewed by trained interviewers in study centres established in Johannesburg, Kimberley, Pretoria, Bloemfontein, Cape Town and Port Elizabeth. RESULTS: A convincing history of asbestos exposure was obtained in the overwhelming majority of cases (only 5 cases had unlikely asbestos exposure). Twenty-three subjects had worked on Cape crocidolite mines, 3 at Penge (an amosite mine), 3 on mines producing amosite and Transvaal crocidolite and 1 on a Transvaal crocidolite mine. Exclusively environmental exposure accounted for at least 18% of cases; 91% of these cases (20/22 subjects) had had contact with Cape crocidolite. There was a relative paucity of cases linked to amosite and no convincing chrysotile case. Non-asbestos causes occur rarely, if at all, in South Africa. CONCLUSION: The preponderance of crocidolite cases, followed by amosite and then chrysotile cases, is consistent with the view that there is a fibre gradient of mesotheliomagenic potential for South African asbestos (crocidolite > amosite > chrysotile).

Asbestos, Amosite↗
PubMed1998

New therapeutic technique for treatment of uterine leiomyomas using laser-induced interstitial thermotherapy (LITT) by a minimally invasive method.

BACKGROUND AND OBJECTIVE: This study was undertaken to see if uterine leiomyomas would respond to LITT, as had certain other tumours, and leave behind a uterus capable of child bearing. STUDY DESIGN/MATERIALS AND METHODS: Preliminary research to determine laser power and energy requirements to coagulate leiomyomas was carried out on such tumours at the time of myomectomy or hysterectomy. The information gleaned permitted subsequent volunteer patients to be treated by a minimally invasive route. LITT was employed to treat 300 patients, 293 of them with the KTP/YAG laser with a bare fibre laparoscopically or through the hysteroscope. The remaining seven were treated with the Diode laser, five of them being treated percutaneously with fibre splitter and four fibres. RESULTS: Symptomatic patients (300) with 950 myomas between them were treated. Follow-up has been between 6 months and 6 years. No significant complications occurred, and the procedure(s) were successful in 294 patients. CONCLUSIONS: It is the treatment of choice for those leiomyomas that are difficult to remove because of their size or position. Fertility is enhanced, oestrogen receptors and epidermal growth factor are destroyed, and healing occurs without scarring.

Adult↗
PubMed1998

The unfolded protein response: an intracellular signalling pathway with many surprising features.

The unfolded protein response (UPR) is an intracellular signalling pathway--originating in the endoplasmic reticulum (ER) and leading to the cell nucleus--that controls transcription of genes encoding ER-resident proteins. Recent developments in this field show that this pathway utilizes unique regulatory mechanisms, including translational attenuation and a regulated mRNA splicing step catalysed by a bifunctional transmembrane kinase/endoribonuclease and tRNA ligase. This review describes the characterization of the UPR signalling pathway, focusing on the novel regulatory mechanisms that it has revealed.

Endoplasmic Reticulum↗