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Biomedical subjects

E Hughes

Publications and source records attributed to E Hughes.

At least 19 recordsLinked to original sources
PubMed2006

Intra-uterine insemination for unexplained subfertility.

BACKGROUND: Intra-uterine insemination (IUI) is a widely used fertility treatment for couples with unexplained subfertility. Although IUI is less invasive and less expensive than in vitro fertilisation (IVF), the safety of IUI in combination with ovarian hyperstimulation (OH) is debated. The main concern about IUI treatment with OH is the increase in multiple pregnancy rates. OBJECTIVES: To determine whether for couples with unexplained subfertility IUI improves the live birth rate compared with timed intercourse (TI), both with and without ovarian hyperstimulation. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorder and Subfertility Group Trials Register (searched March 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2005, Issue 4), MEDLINE (1966 to November 2005), EMBASE (1980 to November 2005), SCIsearch and reference lists of articles. Authors of identified studies were contacted for missing or unpublished data. SELECTION CRITERIA: Truly randomised controlled trials (RCTs) with at least one of the following comparisons were included: --IUI versus TI, both in a natural cycle; --IUI versus TI, both in a stimulated cycle; --IUI in a natural cycle versus IUI in a stimulated cycle; --IUI with OH versus TI in natural cycle; --IUI in a natural cycle versus TI with OH. Only couples with unexplained subfertility were included. DATA COLLECTION AND ANALYSIS: Quality assessment and data extraction were performed independently by two review authors. Outcomes were extracted and the data were pooled. Subgroup analyses and sensitivity analyses were done where possible. MAIN RESULTS: In the six trials where IUI was compared with TI, both in stimulated cycles, there was evidence of an increased chance of pregnancy (six RCTs, 517 women: OR 1.68, 95% CI 1.13 to 2.50). A significant increase in pregnancy rate was also found for women where IUI with OH was compared with IUI in a natural cycle (three RCTs, 415 women: OR 2.33, 95% CI 1.46 to 3.71). However, the trials provided insufficient data to investigate the impact of IUI with or without OH on several important outcomes including live birth, multiple pregnancies, miscarriage and risk of ovarian hyperstimulation. There was no evidence of a difference in pregnancy rate for IUI with OH compared with TI in a natural cycle (one RCT, 51 women: OR 4.05, 95% CI 0.39 to 41.87). No RCTs were found for the other two comparisons. AUTHORS' CONCLUSIONS: There is evidence that IUI with OH increases the live birth rate compared to IUI alone. The likelihood of pregnancy was also increased for treatment with IUI compared to TI both in stimulated cycles. There is insufficient data on multiple pregnancies and other adverse events for treatment with OH. Therefore, couples should be fully informed about the risks of IUI and OH as well as alternative treatment options.

Female↗
PubMed2006

Measles-associated encephalopathy in children with renal transplants.

Two children, boys of 8 and 13 years, presented with measles-associated encephalopathy several years after kidney transplantation for congenital nephrotic syndrome. In the absence of prior clinical measles, the neurological symptoms initially eluded diagnosis, but retrospective analysis of stored samples facilitated the diagnosis of measles-associated encephalopathy without recourse to biopsy of deep cerebral lesions. Each had received a single dose of measles mumps and rubella vaccine before 12 months of age. Prior vaccination, reduction of immunosuppression and treatment with intravenous immunoglobulin and ribavirin may have contributed to their survival. Persistent measles virus RNA shedding, present in one child, was not controlled by treatment with i.v. ribavirin. Two years later, both patients continue to have functioning allografts with only minimal immunosuppression. These cases illustrate the difficulty in diagnosing measles-associated encephalopathy in the immunocompromised host, even in the era of molecular diagnostics, and highlight the renewed threat of neurological disease in communities with incomplete herd immunity.

Adolescent↗
PubMed2005

Marked differences in the IGF system that are associated with migration in comparable populations of Gujaratis living in Sandwell, UK, and Gujarat, India.

AIMS/HYPOTHESES: We previously reported independent links between the IGF system and the development of impaired glucose tolerance and cardiovascular risk. This study tests the hypothesis that the lifestyle change which accompanies population migration, with attendant increases in cardiovascular risk, is reflected by changes in the IGF system. MATERIALS AND METHODS: We compared a specific Gujarati community in Sandwell, UK (n=205), with people still resident in the same villages of origin near Navsari, India (n=246). We performed anthropometry and measured fasting plasma insulin, IGF-I, insulin-like growth factor binding protein (IGFBP)-1 and IGFBP-3. RESULTS: Daily calorie intake, BMI and WHR were significantly higher in UK Gujaratis than in Indian Gujaratis. IGFBP-1 was significantly lower in UK migrants (mean 29.5 [95% CI 25.9-33.0] vs 56.5 [50.6-62.5] microg/l; F=48.4, p<0.001). Conversely, fasting insulin, IGFBP-3 and IGF-I were all higher in UK Gujaratis (mean IGF-I 145.9 [138.1-153.6]ng/ml in UK Gujaratis and 100.9 [94.6-107.3] ng/ml in Navsari Gujaratis; F=76.6, p<0.001). These differences were still apparent when adjustment was made for BMI by location for IGF-I (F=57.4, p<0.001) and IGFBP-3 (F=5.7, p=0.02), but were no longer apparent for IGFBP-1 and insulin. At the population level, the decrease in IGFBP-1 for a given increase in insulin was significantly smaller in UK Gujaratis, suggesting greater hepatic insulin resistance in this group. CONCLUSIONS/INTERPRETATION: Environmental factors have profound effects on circulating IGF system components and on the relationship between IGFBP-1, IGF-I and related metabolic variables. This may have long-term implications for the development of worsening glucose tolerance and cardiovascular disease.

Blood Glucose↗
PubMed2005

Impact of migration on coronary heart disease risk factors: comparison of Gujaratis in Britain and their contemporaries in villages of origin in India.

The causes of the excess coronary heart disease (CHD) risk in South Asian migrants from the Indian subcontinent remain unclear. Comparisons of CHD risk factors amongst South Asian migrants living in Britain with those of the general UK population provide only a partial explanation. We compared Gujaratis in Britain with similar, non-migrant Gujaratis in India, to test the hypothesis that differences in CHD risk factors associated with migration would be more informative. Randomly sampled Gujaratis aged 25-79 years living in Sandwell (n = 242) were compared with age-, gender- and caste-matched contemporaries remaining in their villages of origin in Navsari, India (n = 295). Lifestyle indices, food intake and physical activity, were assessed with standardised questionnaires and energy expenditure and metabolic parameters measured. British Gujaratis had higher, mean body mass indices by 6 (4.5-7.4) kg/m(2) mean (95% CI), and greater dietary energy intake, fat intake, blood pressure, fasting serum cholesterol, apolipoprotein B, triglycerides, non-esterified fatty acid (NEFA) and C-reative protein concentrations than Gujaratis in India. Dietary folate and serum folate and Vitamin B(12) were lower and plasma homocysteine was higher in India. Smoking was less prevalent and high-density lipoprotein cholesterol tended to be higher in Britain. Diabetes prevalence was high in both populations and impaired fasting or 2 h post-glucose challenge plasma glucose was even more prevalent in Gujarat. In India, however, where insulin secretion and NEFA were lower diabetes and impaired glucose tolerance were less frequently accompanied by excess metabolic CVD risk factors. In conclusion, exposure to increased fat intake and obesity related to migration is likely to explain the disproportionate combination of established and emerging CHD risk factors prevalent in Gujaratis in Britain. Strategies to improve nutrition and to identify and treat cardiovascular risk factors such as dyslipidaemia and hypertension are urgently required.

Adult↗
PubMed2005

Tubal flushing for subfertility.

BACKGROUND: A possible therapeutic effect of diagnostic tubal patency testing has been debated in the literature for half a century. Further debate surrounds whether oil-soluble or water-soluble contrast media might have the bigger fertility-enhancing effect. Historically a variety of agents have been used to 'flush' the fallopian tubes, although tubal flushing does not currently form part of routine practice in the treatment of fertility delay. OBJECTIVES: To evaluate the effect of flushing a woman's fallopian tubes with oil- or water-soluble contrast media on subsequent fertility outcomes in couples with infertility. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group's specialised register of trials (searched 2 March 2004), MEDLINE (1966 to Mar 2004), EMBASE (1980 to Mar 2004), Biological Abstract (1980 to Mar 2004) and reference lists of articles. SELECTION CRITERIA: All randomised trials where tubal flushing with oil-soluble contrast media or tubal flushing with water-soluble media was compared with one another or with no treatment were considered for inclusion in the review. DATA COLLECTION AND ANALYSIS: Eleven randomised controlled trials were identified and included in this review. All trials were assessed for quality criteria. The studied primary outcome was live birth (and ongoing pregnancy), with secondary outcomes pregnancy, miscarriage, ectopic pregnancy, treatment complications including pain, intravasation of contrast medium, infection and haemorrhage, and image quality. MAIN RESULTS: Tubal flushing with oil-soluble media versus no intervention (three trials including 381 participants) was associated with a significant increase in the odds of live birth (Peto OR 2.98, 95%CI 1.40 to 6.37) and of pregnancy (Peto OR 3.30, 95%CI 2.00 to 5.43). There were no data from RCTs to assess tubal flushing with water-soluble media versus no intervention. For the comparison of tubal flushing with oil-soluble media versus tubal flushing with water-soluble media (six trials including 1,483 participants), the increase in the odds of live birth for tubal flushing with oil-soluble versus water-soluble media (Peto OR 1.49, 95%CI 1.05 to 2.11) was based on two trials where statistical heterogeneity was present and the higher quality trial showed no significant difference; there was no evidence of a significant difference in the odds of pregnancy (Peto OR 1.24, 95%CI 0.97 to 1.57). The addition of oil-soluble media to flushing with water-soluble media (water-soluble plus oil-soluble media versus water-soluble media alone; three trials including 555 participants) showed no evidence of a significant difference in the odds of pregnancy (Peto OR 1.18, 95%CI 0.82 to 1.70) or live birth (Peto OR 1.06, 95%CI 0.64 to 1.77). Adverse event data were only available for the comparison OSCM versus WSCM: OSCM carried a significantly higher chance of intravasation (Peto OR 5.41, 95%CI 2.57 to 11.37) but a significantly lower chance of immediate pain (Peto OR 0.53, 95%CI 0.34 to 0.84), prolonged pain (Peto OR 0.26, 95%CI 0.15 to 0.45) and post-procedure bleeding (Peto OR 0.22, 95%CI 0.15 to 0.31), and no serious adverse events were reported. AUTHORS' CONCLUSIONS: There is evidence of effectiveness of tubal flushing with oil-soluble contrast media in increasing the odds of pregnancy and live birth versus no intervention. The limited evidence of an increase in the odds of live birth from tubal flushing with oil-soluble contrast media versus water-soluble contrast media must be interpreted cautiously. Further robust randomised trials, comparing oil-soluble versus water-soluble media and comparing water-soluble media versus no intervention, would be a useful further guide to clinical practice. Further research is merited to ascertain the mechanism of the fertility enhancing effect of oil-soluble media, as to whether this is a 'tubal flushing' phenomenon, an effect on the intraperitoneal environment, or an implantation enhancing effect on the endometrium.

Contrast Media↗
PubMed2005

Oral anti-oestrogens and medical adjuncts for subfertility associated with anovulation.

BACKGROUND: Infertility due to anovulation is a common problem in women. The first line oral treatment is with anti-oestrogens, such as clomiphene citrate. Unfortunately there may be resistance and alternative and adjunctive treatments have been developed. These include tamoxifen, dexamethasone, bromocriptine and aromatase inhibitors (AIs). OBJECTIVES: To determine the relative effectiveness of anti-oestrogen agents, with or without medical adjuncts, in women with WHO group 2 anovulation. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trial register (searched 5th July 2004), CENTRAL (The Cochrane Library Issue 2 2004), MEDLINE (1966 to June 2004) and EMBASE (1980 to June 2004) for identification of relevant randomised controlled trials (RCTs). Additionally the United Kingdom National Institute for Clinical Excellence (NICE) guidelines and the references of relevant reviews and RCTs were searched. SELECTION CRITERIA: RCTs that compare oral anti-oestrogen agents for ovulation induction (alone or in conjunction with medical adjuncts) in anovulatory subfertility, were considered for inclusion in the review. Metformin and other insulin sensitizing agents were not included. Hyperprolactinaemic infertility was not included. DATA COLLECTION AND ANALYSIS: Data extraction and quality assessment was done independently by two reviewers. The primary outcome was live birth, secondary outcomes were: pregnancy, ovulation, miscarriage, multiple pregnancy, overstimulation, ovarian hyperstimulation syndrome and patient reported adverse effects. MAIN RESULTS: Twelve RCTs were found and included in this review. No trials reported live birth as an outcome. Miscarriage and multiple pregnancy rates were poorly reported. Clomiphene was shown to be effective in increasing pregnancy rate when compared to placebo (fixed OR 5.8, 95% CI 1.6 to 21.5; NNT 5.9, 95% CI 3.6 to 16.7). No evidence of a difference in effect was found between clomiphene and tamoxifen (fixed OR 1.0, 95% CI 0.5 to 2.1). The use of clomiphene in combination with tamoxifen did not find any evidence of effect on pregnancy rate when compared to clomiphene alone (fixed OR 3.3, 95% CI 0.1 to 91.6). The comparison between two AIs (letrozole and anastrozole) did not find any evidence of a difference in effect on pregnancy rate (fixed OR 1.9, 95% CI 0.4 to 8.9). For the intervention of clomiphene plus ketoconazole vs clomiphene no evidence of a difference in effect for pregnancy rate was found (fixed OR 2.4, 95% CI 0.9 to 6.4). For clomiphene plus bromocriptine vs clomiphene no evidence of a difference in effect on pregnancy rate was found (fixed OR 1.0, 95% CI 0.3 to 3.0) rates. However, clomiphene plus dexamethasone treatment resulted in a significant improvement in the pregnancy rate (fixed OR 11.3, 95% CI 5.3 to 24.0; NNT 2.7, 95% CI 2.1 to 3.6) when compared to clomiphene alone as did clomiphene plus pretreatment with combined oral contraceptives (fixed OR 27.2, 95% CI 3.1 to 235.0; NNT 2.0, 95% CI 1.4 to 3.4). AUTHORS' CONCLUSIONS: This review shows evidence supporting the effectiveness of the current first line treatment, clomiphene citrate. No evidence of a difference in effect was found between clomiphene and tamoxifen. The use of dexamethasone as an adjunct to clomiphene therapy appears promising as do combined oral contraceptives. This review has highlighted a gap in the literature on effects of these drugs on outcomes such as miscarriage rate. Evidence in favour of these interventions is flawed. RCTs of adequate power and of high methodological quality are required for the older treatments such as clomiphene, alone and with medical adjuncts, and also for the newer drugs such as the AIs.

Anovulation↗
PubMed2005

"SLANG"--Sensitive Language and the New Genetics--an exploratory study.

SLANG-Sensitive Language and the New Genetics--is a concept that arose out of informal discussions between a number of interested parties, both consumers and professionals, who were becoming increasingly uneasy with some of the language commonly used in medical genetics. Some language choices were felt by the authors to be inappropriate for a variety of reasons. Poor language choice may impede an individual's understanding of a genetic condition or important medical information and the chosen words themselves may simply be perceived as discriminatory and even offensive. SLANG is an important concept to explore partly because literature in this area confirms that language choices in medical settings can be of great significance to both patients and families. Studies have shown how language choices impact on professional practice by, as one example, changing the intended meaning of medical information and affecting individual perception of risk and choice which, in turn, may affect individual or familial well-being. In addition language choice has the power to affect how individuals perceive themselves and are viewed by others. This paper presents the results from our pilot study and discusses the implications for health professionals with particular reference to medical genetics settings.

Choice Behavior↗
PubMed2005

Connecting capitals.

Explore the source record for details and available documents.

Catchment Area, Health↗
PubMed2005

Spectroscopic studies of phospholamban variants in phospholipid bilayers.

Phospholamban (PLB) is a 52 amino acid transmembrane protein found in the sarcoplasmic reticulum of cardiac myocytes, where it regulates the transport of calcium ions by SERCA (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase). This work has shown that the cytoplasmic domain of PLB associates with phospholipid vesicles, possibly with the lipid polar head groups, and, in doing so, undergoes a transition from a random coil to a more helical conformation. These findings support a recent hypothesis that the cytoplasmic domain of PLB acts as a conformational switch, alternating between an orientation that lies across the membrane surface and an upright orientation that associates with the regulatory site of SERCA.

Amino Acid Sequence↗
PubMed2005

Dietary intake and the insulin-like growth factor system: effects of migration in two related populations in India and Britain with markedly different dietary intake.

BACKGROUND: The insulin-like growth factor (IGF) system is implicated in the pathogenesis of diabetes and cardiovascular disease. OBJECTIVE: We report the effects of total energy intake on the IGF system in two populations with markedly different dietary macronutrient intake and cardiovascular event rate. DESIGN, SUBJECTS AND SETTING: Dietary macronutrient intake was measured in a specific Gujarati migrant community in Sandwell, UK (n=205) compared with people still resident in the same villages of origin in India (n=246). Fasting IGF-I, IGF-binding protein (IGFBP)-1 and IGFBP-3, insulin and glucose (0 and 2-hour) were measured. RESULTS: Total energy and total fat intake were higher in UK migrants, as were IGFBP-3 and IGF-I (mean (95% confidence interval): 145.9 (138.1-153.6) vs. 100.9 (94.6-107.3) ng ml(-1); F=76.6, P<0.001). IGFBP-1 was lower in UK migrants (29.5 (25.9-33.0) vs. 56.5 (50.6-62.5) microg l(-1); F=48.4, P<0.001). At both sites, IGF-I correlated positively with total energy (Spearman's rho=0.45, P<0.001) and total fat (rho=0.44, P<0.001) as did IGFBP-3 with total energy (rho=0.21, P<0.05) and fat (rho=0.26, P<0.001). Conversely, in Indian Gujaratis, IGFBP-1 fell with increasing total energy (rho=-0.27, P<0.001) and fat intake (rho=-0.26, P<0.01) but not in UK Gujaratis. Multiple linear regression modelling showed that increasing quartiles of fat intake were associated with higher IGF-I (beta=0.42, P=0.007) independent of age, body mass index, plasma insulin, fatty acids and 2-hour glucose. CONCLUSION: In these genetically similar groups, migration to the UK and adoption of a different diet is associated with marked changes in the IGF system, suggesting that environmental factors profoundly modulate serum concentrations and actions of IGFs.

Blood Glucose↗
PubMed2005

Extensive cervical spinal cord lesion with late foetal presentation.

Neonatal cervical spinal cord injury occurring in the perinatal period is rare but has been described after both traumatic and atraumatic birth. Recently, a case of atraumatic, late third trimester, pre-labour presentation has been described. We report a second such case, but with important diagnostic differences and outcome. This case showed loss of foetal movements late in the third trimester. This was secondary to an extensive cervical lesion with no history of trauma. This emphasizes the need to consider cervical cord lesions when foetal or postnatal movements are reduced, even in the absence of trauma.

Cervical Vertebrae↗
PubMed2004

Measurement of the generalized forward spin polarizabilities of the neutron.

The generalized forward spin polarizabilities gamma(0) and delta(LT) of the neutron have been extracted for the first time in a Q2 range from 0.1 to 0.9 GeV2. Since gamma(0) is sensitive to nucleon resonances and delta(LT) is insensitive to the Delta resonance, it is expected that the pair of forward spin polarizabilities should provide benchmark tests of the current understanding of the chiral dynamics of QCD. The new results on delta(LT) show significant disagreement with chiral perturbation theory calculations, while the data for gamma(0) at low Q2 are in good agreement with a next-to-leading-order relativistic baryon chiral perturbation theory calculation. The data show good agreement with the phenomenological MAID model.

Journal Article↗
PubMed2004

Q2 evolution of the neutron spin structure moments using a 3He target.

We have measured the spin structure functions g(1) and g(2) of 3He in a double-spin experiment by inclusively scattering polarized electrons at energies ranging from 0.862 to 5.058 GeV off a polarized 3He target at a 15.5 degrees scattering angle. Excitation energies covered the resonance and the onset of the deep inelastic regions. We have determined for the first time the Q2 evolution of Gamma(1)(Q2)= integral (1)(0)g(1)(x,Q2)dx, Gamma(2)(Q2)= integral (1)(0)g(2)(x,Q2)dx, and d(2)(Q2)= integral (1)(0)x(2)[2g(1)(x,Q2)+3g(2)(x,Q2)]dx for the neutron in the range 0.1< or =Q2< or =0.9 GeV2 with good precision. Gamma(1)(Q2) displays a smooth variation from high to low Q2. The Burkhardt-Cottingham sum rule holds within uncertainties and d(2) is nonzero over the measured range.

Journal Article↗
PubMed2002

Tubal flushing for subfertility.

BACKGROUND: A possible therapeutic effect of diagnostic tubal patency testing has been debated in the literature for half a century. Further debate surrounds whether oil-soluble or water-soluble contrast media might have the bigger fertility-enhancing effect. Historically a variety of agents have been used to 'flush' the fallopian tubes, although tubal flushing does not currently form part of routine practice in the treatment of fertility delay. OBJECTIVES: To evaluate the effect of flushing a woman's fallopian tubes with oil- or water-soluble contrast media on subsequent pregnancy outcomes in couples with infertility. SEARCH STRATEGY: The search strategy of the Menstrual Disorders and Subfertility Group and a recent search of electronic databases completed in December 2001 was used for the identification of relevant randomised controlled trials. SELECTION CRITERIA: All randomised trials where tubal flushing with oil-soluble contrast media or tubal flushing with water-soluble media was compared with one another or with no treatment were considered for inclusion in the review. DATA COLLECTION AND ANALYSIS: Eight randomised controlled trials were identified and included in this review. A further one randomised controlled trial is ongoing. All trials were assessed for quality criteria. The studied outcomes were pregnancy, live birth (and ongoing pregnancy), miscarriage, ectopic pregnancy, treatment complications including pain, intravasation of contrast medium, infection and haemorrhage, and image quality. MAIN RESULTS: Tubal flushing with oil-soluble media versus no intervention was associated with a significant increase in the odds of pregnancy (OR 3.57, 95%CI 1.76-7.23). There were no data from RCTs to assess tubal flushing with water-soluble media versus no intervention. Tubal flushing with oil-soluble media was associated with a significant increase in the odds of live birth versus tubal flushing with water-soluble media (OR 1.49, 95%CI 1.05-2.11) but the odds of pregnancy showed no significant difference (OR 1.23, 95%CI 0.95-1.60) and there was evidence of statistical heterogeneity for these two outcomes. The addition of oil-soluble media to flushing with water-soluble media (water-soluble plus oil-soluble media versus water-soluble media alone) showed no significant difference in the odds of pregnancy (OR 1.16, 95%CI 0.78-1.70) or live birth (OR 1.06, 95%CI 0.64-1.77). REVIEWER'S CONCLUSIONS: There is some evidence of effectiveness of tubal flushing with oil-soluble contrast media in increasing the odds of pregnancy versus no intervention. The limited evidence of an increase in the odds of live birth from tubal flushing with oil-soluble contrast media versus water-soluble contrast media must be interpreted cautiously. Further robust randomised trials, comparing oil-soluble versus water-soluble media and comparing each versus no intervention, are required to provide convincing evidence as to whether the technique should be accepted into widespread clinical practice.

Contrast Media↗
PubMed2002

Assessing pain behaviour of low-back pain patients in real time: concurrent validity and examiner sensitivity.

Several systems for measuring pain behaviour have been developed for clinical settings. The present study reports on a real-time system for coding five categories of pain behaviour for low-back pain patients: guarding, touching, sounds, words, and facial expression. Unique features of the system are the use of refined measures of facial expression and integration of the measurements with a standardized physical examination. 176 sub-acute and chronic low-back pain patients underwent a physical examination while their pain behaviour was coded. Concurrent measures of subjective pain, medically-incongruent signs, and independent global ratings of pain behaviour were taken. Analyses indicated that the pain behaviours, particularly guarding and facial expression, varied systematically with the alternative measures, supporting the concurrent validity of the behaviour observation system. While pain behaviours, especially use of words and facial expressions, were significantly associated with the examiners' independent ratings, the strength of the associations suggested that, in the absence of direct training, examiners' performance was relatively poor. Implications for training of clinicians in detecting pain behaviour are discussed.

Adult↗
PubMed2002

Inhibition of toxicity and protofibril formation in the amyloid-beta peptide beta(25-35) using N-methylated derivatives.

Beta (25-35) is a fragment of beta-amyloid that retains its wild-type properties. N-methylated derivatives of beta(25-35) can block hydrogen bonding on the outer edge of the assembling amyloid, so preventing the aggregation and inhibiting the toxicity of the wild-type peptide. The effects are assayed by Congo Red and thioflavin T binding, electron microscopy and an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] toxicity assay. N-methyl-Gly-25 has similar properties to the wild- type, while five other methylation sites have varying effects on prefolded fibrils and fibril assembly. In particular, N-methyl-Gly-33 is able to completely prevent fibril assembly and reduces the toxicity of prefolded amyloid. With N-methyl-Leu-34 the fibril morphology is altered and toxicity reduced. A preliminary study of beta(25-35) structure in aqueous solution was made by small-angle neutron scattering (SANS). The protofibrillar aggregates are best described as a disc of radius 140 A and height 53 A (1 A = 0.1 nm), though the possibility of polydisperse aggregates cannot be ruled out. No aggregates form in the presence of N-methyl-Gly-33. We suggest that the use of N-methylated derivatives of amyloidogenic peptides and proteins could provide a general solution to the problem of amyloid deposition and toxicity and that SANS is an important technique for the direct observation of protofibril formation and destruction in solution.

Alzheimer Disease↗
PubMed2001

Precision measurement of the spin-dependent asymmetry in the threshold region of 3He(e, e').

We present the first precision measurement of the spin-dependent asymmetry in the threshold region of 3He(e,e') at Q2 values of 0.1 and 0.2 (GeV/c)2. The agreement between the data and nonrelativistic Faddeev calculations which include both final-state interactions and meson-exchange current effects is very good at Q2 = 0.1 (GeV/c)2, while a small discrepancy at Q2 = 0.2 (GeV/c)2 is observed.

Journal Article↗