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Biomedical subjects

N Lawrence

Publications and source records attributed to N Lawrence.

At least 19 recordsLinked to original sources
PubMed2005

Gene-flow between populations of cotton bollworm Helicoverpa armigera (Lepidoptera: Noctuidae) is highly variable between years.

Both large and small scale migrations of Helicoverpa armigera Hübner in Australia were investigated using AMOVA analysis and genetic assignment tests. Five microsatellite loci were screened across 3142 individuals from 16 localities in eight major cotton and grain growing regions within Australia, over a 38-month period (November 1999 to January 2003). From November 1999 to March 2001 relatively low levels of migration were characterized between growing regions. Substantially higher than average gene-flow rates and limited differentiation between cropping regions characterized the period from April 2001 to March 2002. A reduced migration rate in the year from April 2002 to March 2003 resulted in significant genetic structuring between cropping regions. This differentiation was established within two or three generations. Genetic drift alone is unlikely to drive genetic differentiation over such a small number of generations, unless it is accompanied by extreme bottlenecks and/or selection. Helicoverpa armigera in Australia demonstrated isolation by distance, so immigration into cropping regions is more likely to come from nearby regions than from afar. This effect was most pronounced in years with limited migration. However, there is evidence of long distance dispersal events in periods of high migration (April 2001-March 2002). The implications of highly variable migration patterns for resistance management are considered.

Analysis of Variance↗
PubMed2003

Relation between insulin kinetics and insulin sensitivity in pregnancy.

BACKGROUND: Different time-concentration profiles of plasma insulin following insulin modification of a frequently sampled intravenous glucose-tolerance-test (FSIVGTT) were observed in a study investigating maternal metabolism and fetal macrosomia. We aimed to investigate whether these differences were related to the volume of distribution of insulin, insulin clearance, or both. DESIGN: Forty-four women were studied between 33 and 35 weeks' gestation using an insulin-modified FSIVGTT. Specific insulin was assayed with an enzyme-linked immunosorbent assay. Insulin sensitivity was calculated using the minimal model and the homeostasis model assessment (HOMA). The volume of distribution and clearance of insulin were calculated from measurements between 2 and 155 min after insulin modification using a one-compartment model. RESULTS: In accordance with the method for deriving the volume of distribution, there was a significant negative correlation between the increment in insulin concentration and the volume of distribution (rho=-0.92, P<0.0001). The insulin increment was also related negatively to the clearance of insulin (rho=-0.88, P<0.0001). There was a significant correlation between the volume of distribution and both the insulin sensitivity index (rho=0.56, P<0.0001) and HOMA-%S (rho=0.30, P=0.048), and between the clearance of insulin and both the insulin sensitivity index (rho=0.83, P<0.0001)) and HOMA-%S (rho=0.34, P=0.025). CONCLUSION: The different time-concentration profiles of plasma insulin resulted from differences in the volume of distribution and clearance of insulin. There was a correlation between insulin kinetics and the insulin sensitivity index. Further research is required to investigate possible mechanisms by which insulin kinetics may be related to insulin sensitivity.

Enzyme-Linked Immunosorbent Assay↗
PubMed2003

A sensitive radioimmunoprecipitation assay for assessing the clinical relevance of antibodies to IFN beta.

BACKGROUND: Some multiple sclerosis (MS) patients treated with interferon beta (IFN beta) develop antibodies to the drug. Neutralising antibody (NAB) assays for IFN beta are expensive and the clinical relevance of the results has been debated. OBJECTIVE: To establish a cheap, sensitive, and reliable assay for antibodies to (125)I-IFN beta, and to correlate levels of antibodies with clinical response to IFN beta treatment. METHODS: We established a radioimmunoprecipitation assay (RIPA) using (125)I-IFN beta. We tested NAB positive sera, healthy control sera, and serial samples of 33 IFN beta-1b treated MS patients from the Vancouver cohort of the Berlex pivotal trial who had a high incidence of NABs. RESULTS: We found that the RIPA was highly sensitive for the detection of antibodies to IFN beta-1a and -1b, and that there was a strong correlation between reactivity of NAB positive sera for (125)I-IFN beta-1b and for (125)I-IFN beta-1a. The RIPA was more sensitive and consistent than the NAB. Moreover, there was a trend towards poorer MRI outcomes in RIPA positive patients, but not in NAB-positive patients. CONCLUSIONS: The RIPA assay is sensitive and easy to perform. It should be of value in assessing the clinical impact of IFN beta antibodies, and its use could help target expensive INF beta treatments to those who will respond best.

Antibodies↗
PubMed2001

Notch signaling targets the Wingless responsiveness of a Ubx visceral mesoderm enhancer in Drosophila.

BACKGROUND: Members of the Notch family of receptors mediate a process known as lateral inhibition that plays a prominent role in the suppression of cell fates during development. This function is triggered by a ligand, Delta, and is implemented by the release of the intracellular domain of Notch from the membrane and by its interaction with the protein Suppressor of Hairless [Su(H)] in the nucleus. There is evidence that Notch can also signal independently of Su(H). In particular, in Drosophila, there is evidence that a Su(H)-independent activity of Notch is associated with Wingless signaling. RESULTS: We report that Ubx(VM)B, a visceral mesoderm-specific enhancer of the Ubx gene of Drosophila, is sensitive to Notch signaling. In the absence of Notch, but not of Su(H), the enhancer becomes activated earlier and over a wider domain than in the wild type. Furthermore, the removal of Notch reduces the requirement for Disheveled-mediated Wingless signaling to activate this enhancer. This response to Notch is likely to be mediated by the dTcf binding sites in the Ubx(VM)B enhancer. CONCLUSIONS: Our results show that, in Drosophila, an activity of Notch that is likely to be independent of Su(H) inhibits Wingless signaling on Ubx(VM)B. A possible target of this activity is dTcf. As dTcf has been shown to be capable of repressing Wingless targets, our results suggest that this repressive activity may be regulated by Notch. Finally, we suggest that Wingless signaling is composed of two steps, a down-regulation of a Su(H)-independent Notch activity that modulates the activity of dTcf and a canonical Wingless signaling event that regulates the activity of Armadillo and its interaction with dTcf.

Animals↗
PubMed2001

Wnt signalling: a theme with nuclear variations.

Wnt proteins are involved in a large number of events during development and disease. The crucial element in the transduction of the signal elicited by Wnt is the state and activity of beta-catenin. There are two pools of beta-catenin, one associated with cadherins at the cell surface and a soluble one in the cytolasm, whose state and concentration are critical for Wnt signalling. In the absence of Wnt, the cytoplasmic pool is low due to targetted degradation of beta-catenin. Upon Wnt signalling, beta-catenin is stabilized. As a consequence, it can access the nucleus where it interacts with members of the Tcf family of transcription factors to modulate the expression of defined targets. Recent reports indicate that, in addition to Tcfs, beta-catenin can interact with other nuclear proteins raising the possibility that Wnt signalling has a wider modulatory effect on transcription than is mediated by its interactions with Tcfs. BioEssays 23:311-318, 2001.

Animals↗
PubMed2001

The efficacy of powered liposuction.

BACKGROUND: Powered liposuction is a relatively new innovation for more efficient removal of adipose tissue. OBJECTIVE: To evaluate the effectiveness of powered liposuction in removing adipose tissue when compared to traditional liposuction. METHODS: Four powered liposuction devices were evaluated in the power on mode vs. the power off. The fat extracted in each of these modes was measured in a mucous specimen trap. RESULTS: There was increased fat extraction in the powered mode for all instruments. The increased rate of fat extraction varied from 20 to 45% between instruments. the overall increased extraction in powered vs. nonpowered mode was 30%. CONCLUSION: The powered liposuction devices tested significantly increase the efficacy of subcutaneous fat removal during liposuction.

Abdomen↗
PubMed2000

Effects of growth hormone treatment on very-low density lipoprotein apolipoprotein B100 turnover in adult hypopituitarism.

Adult hypopituitarism is associated with hyperlipidemia, mainly due to an increase of very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) levels. Recent studies have shown that such patients exhibit increased hepatic secretion of VLDL apolipoprotein B100 (VLDL apo B100). To examine the effects of growth hormone (GH) replacement on VLDL apo B100 turnover, 13 GH-deficient hypopituitary patients (8 women and 5 men; aged 47 +/- 3 years, mean +/- SEM; body mass index [BMI], 30 +/- 2 kg/m2) entered a double-blind placebo-controlled study for 6 months (GH 0.125 IU/kg/wk for 4 weeks, and then 0.25 IU/kg/wk). GH was subsequently used in all patients for a further 6 months. A 6-hour [1-13C] leucine infusion was administered at baseline and at 6 months. The secretion rate of VLDL apo B100 was derived by kinetic analysis following quantitation of isotopic enrichment by gas chromatography/mass spectrometry. The GH-treated group (6 patients) demonstrated a similar fractional secretion rate (FSR) for VLDL apo B100 at 0 and 6 months. The pool size and absolute secretion rate (ASR) also were unaffected significantly by GH therapy. No significant changes were observed in the placebo group (7 patients). Treatment with GH for 6 months caused an increase in the high-density lipoprotein (HDL) cholesterol concentration (13 patients, 1.27 +/- 0.13 v 1.16 +/- 0.10 mmol/L, respectively, P = .05), whereas total cholesterol and triglyceride concentrations did not change. Nonesterified fatty acids (NEFAs) increased during GH therapy (471 +/- 43 micromol/L at 6 months v 349 +/- 49 micromol/L at baseline, P < .0005). The data suggest that GH does not affect VLDL apo B100 turnover in a significant way.

Adult↗
PubMed2000

New and emerging treatments for photoaging.

It is easy to become too busy treating the sequelae of photoaging, actinic keratoses, and skin cancers to discuss prevention adequately with patients. With children, sun-protective measures and sunscreen information should be the main therapeutic intervention. In any young adult with an actinic keratosis or skin cancer, topical and resurfacing treatments should be considered. In older patients with fragile skin and solar purpura, reversal of photodamage can have a positive effect on daily functioning.

Adult↗
PubMed2000

The prevalence of polycystic ovaries in women with a history of gestational diabetes.

OBJECTIVE: Women with a history of gestational diabetes mellitus (GDM) and women with polycystic ovary syndrome (PCOS) both demonstrate abnormalities in insulin action and secretion, and both are at increased risk of developing type 2 diabetes. To determine whether these similarities reflect a common pathophysiological basis, we examined the prevalence of ultrasound-based polycystic ovarian morphology in a large multiethnic group of women with a history of GDM and a group of women who had normal glucose tolerance during pregnancy. PATIENTS AND DESIGN: We studied 91 women with previous GDM (48 European, 20 South Asian, 10 Afro-Caribbean and 13 of other or mixed ethnicity) and 73 normoglycaemic control women (56 European, one South Asian, 14 Afro-Caribbean and two of other or mixed ethnicity), a median (interquartile range) of 20 (11-36) and 29 (17-49) months postpartum, respectively. A detailed history was taken, and the prevalence of PCO morphology on ultrasound scan was assessed. Fasting lipids, insulin, glucose status, gonadotrophins and testosterone were measured. Estimates of beta-cell function (%B) and insulin sensitivity (%S) were derived using the HOMA algorithm. RESULTS: Women with previous GDM had higher fasting glucose (5.4 (4. 8-6.0) vs. 4.7 (4.4-5.0) mmol/l, P<0.0001) and features reminiscent of syndrome X: higher BMI (26.4 (22.8-31.4) vs. 23.8 (21. 0-27.5) kg/m2, P = 0.002), waist/hip ratio (0.82 (0.79-0.88) vs. 0. 77 (0.73-0.81), P<0.0001), fasting insulin (165 (68-299) vs. 54 (24-156) pmol/l, P<0.0001), triglycerides (1.1 (0.8-1.6) vs. 0.8 (0.6-1.1) mmol/l, P<0.0001) and lower insulin sensitivity (%S) (27 (16-62) vs. 86 (34-139)%, P<0.0001) compared to control women. The prevalence of PCO was higher in the previous GDM group than in the control subjects (47/91 (52%) vs. 20/73 (27%), chi2 = 9.86, P = 0. 002 overall, odds ratio 2.7, P = 0.007 by logistic regression allowing for ethnicity). There was no difference in any metabolic parameter between the post-GDM PCO group and the post-GDM normal ovaries group, but irregular cycles were more prevalent in the PCO group (22/47 (47%) vs. 9/44 (21%), chi2 = 7.03, P = 0.008). CONCLUSIONS: We found a higher prevalence of polycystic ovarian morphology in women with a history of gestational diabetes. Among the women with previous gestational diabetes, irregular cycles were more prevalent in the PCO group than in the women with normal ovarian morphology, but no other differences in endocrine or metabolic parameters were detected. These findings confirm an association between PCO and gestational diabetes and suggest that women with gestational diabetes display metabolic abnormalities irrespective of ovarian morphology.

Blood Glucose↗
PubMed2000

Recombinant chimeric proteins generated from conserved regions of Plasmodium falciparum merozoite surface protein 2 generate antiparasite humoral responses in mice.

The merozoite surface protein 2 of P. falciparum is highly polymorphic in nature, but has regions of almost complete conservation at its N- and C-termini. We produced a chimeric recombinant protein comprising these regions only (hereafter termed NC). Mice immunized with the NC antigen produce antibodies at levels comparable to those immunized with 1624, a full-length recombinant protein representing MSP2 from P. falciparum. Antisera raised against NC recognized P. falciparum schizonts by IFA and a P. falciparum protein of Mr 45 kDa by Western blot. However, antibody specificities were observed to differ between anti-NC and anti-1624 sera, and this resulted in differences in parasite recognition, despite similar levels of antibodies having been produced. The response to the NC antigen was also shown to be restricted in some mice (H2-d), but this was overcome by including appropriate T-cell help, which was accomplished by creating recombinant protein chimeras that contained NC and T-helper epitopes from Tetanus toxoid, or MSP119 from P. berghei.

Adolescent↗
PubMed2000

The efficacy of external ultrasound-assisted liposuction: a randomized controlled trial.

BACKGROUND: Use of high-intensity, high-frequency external ultrasound before liposuction has been reported to enhance the ease of fat extraction, increase the amount of fat extracted, and decrease patient discomfort during liposuction. OBJECTIVE: The purpose of this study was to compare the effect of application of high-intensity continuous wave ultrasound to extremely low-intensity ultrasound (placebo) prior to tumescent liposuction. METHODS: A total of 19 patients (25 sites) completed the double-blind study. We used a split treatment area design so that each patient could serve as their own control. After tumesing the treatment area, a 3 W/cm2 continuous wave 1 MHz ultrasound was applied for 10 minutes. The placebo control was treated with 0.3 W/cm2 1 MHz for 10 minutes. Traditional tumescent liposuction followed ultrasound application. Doctors completed a visual analog scale rating the following: rate of extraction, degree of resistance to cannula movement, and color of fat. Patients also completed a questionnaire after the procedure and at 1 month postoperatively. Histologic samples of the fat treated with external ultrasound were taken from two patients. RESULTS: In 14 of 19 patients the doctors graded either no difference between treatment and control sides or found a better response on the nontreated side in rate of fat removal and resistance to cannula advancement giving a P value of .0096. Only 5 of 19 aspirates were graded as differing in redness between treatment and control sides. Four of these were more red on the control side and one was more red on the treatment side. Therefore 15 of 19 had no better result with treatment, giving a P value of .0022. Seven patients graded the sensation during suctioning and/or postoperative course as better on the control side, four graded these variables as better on the treatment side, four showed no difference between the two sides, and four had mixed results. This gives only 4 of the 19 patients showing any advantage in treatment with a P value of .0022. CONCLUSION: When the placebo effect is eliminated, there is no advantage to the application of external ultrasound prior to liposuction.

Adipose Tissue↗
PubMed2000

Structural requirements for notch signalling with delta and serrate during the development and patterning of the wing disc of Drosophila.

The delta and Serrate proteins interact with the extracellular domain of the Notch receptor and initiate signalling through the receptor. The two ligands are very similar in structure and have been shown to be interchangeable experimentally; however, loss of function analysis indicates that they have different functions during development and analysis of their signalling during wing development indicates that the Fringe protein can discriminate between the two ligands. This raises the possibility that the signalling of delta and Serrate through Notch requires different domains of the Notch protein. Here we have tested this possibility by examining the ability of delta and Serrate to interact and signal with Notch molecules in which different domains had been deleted. This analysis has shown that EGF-like repeats 11 and 12, the RAM-23 and cdc10/ankyrin repeats and the region C-terminal to the cdc10/ankyrin repeats of Notch are necessary for both delta and Serrate to signal via Notch. They also indicate, however, that delta and Serrate utilise EGF-like repeats 24-26 of Notch for signalling, but there are significant differences in the way they utilise these repeats.

Amino Acid Sequence↗
PubMed2000

dTcf antagonises Wingless signalling during the development and patterning of the wing in Drosophila.

Members of the Tcf family of HMG box-containing transcriptional regulators mediate Wnt signalling in the nucleus. Current models suggest that in the absence of Wnt signalling, Tcf interacts with the repressor protein Groucho and suppresses the expression of Wnt targets. Wnt signalling leads to increases in the level of cytoplasmic beta catenin, which enters the nucleus, displaces Tcf from Groucho and leads to transcriptional activation. In order to test this model we have studied the effects of Drosophila Tcf (dTcf) on signalling by Wingless, a Drosophila member of the Wnt family. We show that overexpression of wild-type dTcf during the development and patterning of the wing antagonises Wingless signalling. Furthermore, increases in the concentration of Armadillo, the Drosophila homologue of beta catenin, do not appear to be sufficient to trigger the change from antagonism to activation. This leads us to suggest that the inactivation of the repressive activity of dTcf requires the activity of Wingless in a manner that is independent of Armadillo. We observe that a Groucho molecule devoid of the WD40 repeats can interact with dTcf and acts as a dominant repressor of Wingless signalling in vivo and in vitro. Coexpression of this molecule with dTcf however, does not lead to enhancement of the repressive effects of dTcf alone. This observation suggests that repression by dTcf might not simply be mediated by an interaction with Groucho but that dTcf may have an intrinsic repressive activity that has to be antagonised by Wingless signalling.

Animals↗
PubMed1999

Ultrasonic-assisted liposuction. Internal and external.

UAL has not provided the promised ideal of "fat dissolution without surgery." In extremely fibrous areas and second procedure liposuction, internal UAL may be a valuable tool once it is further perfected. UAL equipment continues to evolve and as it improves we hope to see a better safety profile, a mechanism for smaller entrance sites, and greater time efficiency in the procedure.

Adipose Tissue↗