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Biomedical subjects

R Chapman

Publications and source records attributed to R Chapman.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Fatal CMV pneumonia associated with steroid therapy after autologous transplantation in patients previously treated with fludarabine.

Fludarabine has been associated with an increased risk of opportunistic infections, possibly related to the induction of profound CD4+ lymphopenia. We observed two cases of cytomegalovirus pneumonia (CMV-IP) in a total of nine patients over a 5-year period who had previously received fludarabine and who proceeded to autografting. Both patients also received steroids post-transplant. CMV-IP was observed in one of 104 other autograft recipients over this time who had not received prior fludarabine. This observation suggests that the combination of fludarabine pre-transplant and steroids post-transplant may increase the risk of invasive CMV disease in autograft recipients.

Adult↗

Intracellular signaling from the endoplasmic reticulum to the nucleus.

Cells respond to an accumulation of unfolded proteins in the endoplasmic reticulum (ER) by increasing transcription of genes encoding ER resident proteins. The information is transmitted from the ER lumen to the nucleus by an intracellular signaling pathway called the unfolded protein response (UPR). Recent work has shown that this signaling pathway utilizes several novel mechanisms, including translational attenuation and a regulated mRNA splicing step. In this review we aim to integrate these recent advances with current knowledge about maintenance of ER composition and abundance.

Animals↗

Hospital management decision support: a balanced scorecard approach.

Hospital management teams receive voluminous data from a wide variety of sources, but are unable to distill the essential data they require to make good decisions. We have used a methodology, which helps teams define and use important management data coupled with an information system that makes this data accessible. Results of our evaluation indicate that the process of developing a Balanced Scorecard indicator system helps management teams to define meaningful strategic objectives and measurable performance indicators. The framework combined with the information acts as an integrating force, providing a shared understanding of the unit's goals. We conclude that a customized decision support system, which integrates multiple measures in a balanced Scorecard framework, is a powerful tool for enabling complex decision making by a management team.

Cardiovascular Diseases↗