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E Miller

Publications and source records attributed to E Miller.

At least 217 records · Page 12Linked to original sources
PubMed1995

Increased autoantibody titers against epitopes of oxidized LDL in LDL receptor-deficient mice with increased atherosclerosis.

Increasing evidence indicates that immune processes modulate atherogenesis. Oxidized LDL (Ox-LDL) is immunogenic, and autoantibodies recognizing epitopes of Ox-LDL have been described in plasma and in atherosclerotic lesions of several species. To determine whether the titer of such autoantibodies correlates with the extent of atherosclerosis, we followed the development of antibodies against malondialdehyde-lysine, an epitope of Ox-LDL, in two groups of LDL receptor-deficient mice for 6 months. One group was fed an atherogenic diet (21% fat and 0.15% cholesterol) that resulted in marked hypercholesterolemia and extensive aortic atherosclerosis; the other group was fed regular rodent chow (4% fat) that did not alter plasma cholesterol levels and induced minimal atherosclerosis. Autoantibody titers significantly increased over time in the group on the atherogenic diet, whereas they remained constant in the chow-fed group. When data from both groups were pooled, a significant correlation was found between the autoantibody titers and the extent of atherosclerosis (r = .61, P < .01). Autoantibody titers also correlated with plasma cholesterol levels (r = .48, P < .05). These results suggest that the rise in autoantibody titers to an epitope of Ox-LDL in this murine model is partially determined by the extent of atherosclerosis but could also be influenced by the degree of hypercholesterolemia or other factors that may influence lipid peroxidation.

Animals↗
PubMed1995

Effect of the antioxidant N,N'-diphenyl 1,4-phenylenediamine (DPPD) on atherosclerosis in apoE-deficient mice.

Apolipoprotein (apo) E-deficient mice develop atherosclerotic lesions that contain epitopes formed during the oxidative modification of lipoproteins, and they demonstrate high titers of circulating autoantibodies against such epitopes, suggesting that this murine strain may provide a model to investigate the atherogenic mechanisms of oxidized lipoproteins (Palinski et al, Arterioscler Thromb. 1994; 14:605-616). To test the hypothesis that lipoprotein oxidation contributes to lesion formation in apoE-deficient mice, we studied the effect of the antioxidant N,N'-diphenyl 1,4-phenylenediamine (DPPD) in mice fed a high-fat diet containing 0.15% cholesterol. Animals were divided into two subgroups matched for sex and plasma cholesterol levels, and DPPD (0.5% wt/wt) was added to the diet of one subgroup. Throughout the 6 months of intervention, DPPD treatment had no significant effect on plasma cholesterol. Plasma levels of DPPD at the end of the experiment were 33.1 mumol/L. As judged by resistance to loss of polyunsaturated fatty acids, lipoproteins (d < 1.019 g/mL) from DPPD-treated animals showed greater resistance to copper-induced oxidation than lipoproteins from control animals. In addition, there was a greater than twofold prolongation of the lag time in the formation of conjugated dienes in the LDL and IDL fractions of DPPD-treated mice. Atherosclerosis was significantly reduced, by 36% in the DPPD-treated mice (14.0 +/- 4.53% of aortic surface area versus 21.9 +/- 11.6%; n = 32; P < .02). These results are consistent with the hypothesis that lipoprotein oxidation contributes to atherogenesis in apoE-deficient mice. However, further studies with other antioxidants are needed to validate this hypothesis.

Animals↗
PubMed1995

Immunological evidence for the presence of advanced glycosylation end products in atherosclerotic lesions of euglycemic rabbits.

Atherosclerosis is known to be accelerated in diabetic patients, but the mechanisms of this acceleration are poorly understood. Nonenzymatic glycosylation of long-lived proteins results in the formation of advanced glycosylation end products (AGEs), which are extensively cross-linked and could contribute to atherogenesis. Oxidative modification of LDL is also an important process in atherogenesis. In vitro evidence suggests that hyperglycemia may enhance lipid peroxidation, and conversely, that increased lipid peroxidation may enhance AGE formation. If such interactions occur in vivo, we hypothesized that AGE should be found in atherosclerotic lesions of euglycemic LDL receptor-deficient rabbits in areas rich in lipids and oxidized lipoproteins. To demonstrate the presence of AGEs, we developed antisera against a specific "model" compound of AGE, 2-furoyl-4(5)-(2-furanyl)-1H-imidazole (FFI) by using FFI-hexanoic acid (FFI-HA)-protein adducts as the antigen and against AGEs in general by using AGE-albumin as the antigen. Antisera generated with FFI-HA-protein adducts recognized FFI-HA alone as well as FFI-protein adducts. Native proteins or proteins conjugated with aldehydes formed during lipid peroxidation in vitro were not recognized by these antisera. Immunocytochemistry with both FFI-specific and AGE-specific antisera revealed the presence of these epitopes in atherosclerotic lesions of euglycemic LDL receptor-deficient rabbits but not in normal aortic tissues. AGE epitopes within atherosclerotic lesions were predominantly found in similar locations as epitopes generated during modification of the lipoproteins by oxidation, consistent with the hypothesized interactions between oxidation and glycosylation. Indirect evidence in support of the in vivo presence of FFI-like structures was also obtained by the observation that both diabetic and euglycemic human subjects contained autoantibodies that recognize FFI-protein adducts. Taken together, these data provide immunological evidence for the in vivo presence of FFI-like structures and other AGE-protein adducts in atherosclerotic lesions, even in euglycemic conditions.

Adult↗
PubMed1995

Effects of coregistration of MR to CT images on MR stereotactic accuracy.

Coregistration of different modality imaging serves to increase the ease and accuracy of stereotactic procedures. In many cases, magnetic resonance (MR) stereotaxis is supplanting computerized tomography (CT). The advantages of increased anatomical detail and multiplanar imaging afforded by MR, however, are offset by its potential inaccuracy as well as the more cumbersome and less available nature of its hardware. A system has been developed by one of the authors by which MR imaging can be performed separately without a stereotactic fiducial headring. Then, immediately prior to surgery, a stereotactic CT scan is obtained and software is used to coregister CT and MR images anatomically by matching cranial landmarks in the two scans. The authors examined this system in six patients as well as with the use of a lucite phantom. After initially coregistering CT and MR images, six separate anatomical (for the patients) and eight artificial (for the phantom) targets were compared. With coregistration, in comparison to CT fiducial scans, errors in each axis are less than or equal to 1 mm using the Cosman-Roberts-Wells system. In fact, the coregistered images are more accurate than MR fiducial images, in the anteroposterior (p = 0.001), lateral (p < 0.05), and vertical (p < 0.03) planes. Three-dimensional error was significantly less in the coregistered scans than the MR fiducial images (p < 0.005). The coregistration procedure therefore not only increases the case of MR stereotaxis but also increases its accuracy.

Brain↗
PubMed1994

The epidemiology of measles in England and Wales: rationale for the 1994 national vaccination campaign.

An epidemic of between 100,000 and 200,000 cases of measles during 1995 has been predicted in England and Wales. This prediction was based on epidemiological evidence from several sources. Notifications of measles to the Office of Population Censuses and Surveys have risen in 1994, with a high proportion of cases in children aged over 10 years. An increase in the incidence of measles was seen in data from other sources, including laboratory reports of confirmed infections and consultations with general practitioners for new episodes of measles. Antibody tests were performed on saliva and serum from notified cases in several districts. Over three quarters of the notified cases in 1994 that were confirmed occurred in children of school age. The proportion of children aged 7 to 14 years who were susceptible to measles, obtained from studies of the age specific prevalence of antibody, rose from 6.0% (146/2453) in 1986 and 1987 to 9.2% (144/1565) in 1991. Mathematical modelling has predicted that the level of susceptibility anticipated in the school age population in 1995 would have been sufficient to allow a resurgence of measles. Over half of the cases in the resulting epidemic would have occurred in people aged at least 10 years and, because mortality is higher in this older age group, between 30 and 60 deaths would have occurred. A mass campaign to immunise all children of school age is expected to cause an immediate reduction in disease transmission and prevent a substantial toll of morbidity and mortality.

Adolescent↗
PubMed1994

Rubella surveillance to June 1994: third joint report from the PHLS and the National Congenital Rubella Surveillance Programme.

A downward trend in the incidence of acquired rubella in England and Wales was reversed in 1993 when there were local outbreaks. These affected young adult males in particular, especially those living in college residences. Some spread to local antenatal populations occurred. Twenty-five confirmed infections were reported in pregnant women, most of whom were young and in their first pregnancy; this compares with totals of 12 and two in 1991 and 1992, respectively. Reports of congenital rubella have not risen since the 1993 outbreaks. Diagnosis lags behind birth, however, and further evaluation may be needed. Notifications of 14 infants, including one set of triplets, born with congenital infection since the beginning of 1991 have been received. Nine of the 12 mothers were immigrants, and three of these acquired their infection abroad. Data on antibody prevalence have revealed a large pool of susceptible males aged 10 to 25 years, which indicates that outbreaks in males would continue for some years if no action were taken. The national measles and rubella vaccination campaign in schools this month should abolish the difference in susceptibility between boys and girls up to 16 years of age and hasten progress towards the interruption of rubella transmission in the United Kingdom. Susceptibility in girls aged 13 to 14 years rose to 5.8% in 1993 from an average of 3.6% between 1986 and 1992. This suggests that the vaccination of schoolgirls has recently declined, but this component of the selective rubella vaccination programme will be discontinued after the measles and rubella campaign.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Age specific antibody prevalence to parvovirus B19: how many women are infected in pregnancy?

Infection with parvovirus B19 is an important cause of late fetal mortality in the second trimester, and many infections in pregnancy remain undiagnosed. A serological survey stratified by age has been used to estimate the incidence of maternal infection with parvovirus B19 in pregnancy. Serum remaining from specimens submitted for diagnosis from 6864 people of all ages to seven public health laboratories in England was tested for antibody to parvovirus B19. The antibody prevalence rose with age to 45% at 10 years and 60% to 70% in adults. The age specific force of infection was highest in children aged less than 10 years and lowest in adults. Maternal infection with parvovirus B19 is estimated to occur in approximately one pregnancy in 400. It has been estimated that fetal death occurs in 9% of these cases, which suggests that parvovirus B19 may cause more than 150 fetal deaths in England and Wales each year. Testing for evidence of recent infection with parvovirus B19 should be considered for unexplained cases of fetal hydrops in the second trimester, especially in years of parvovirus B19 epidemics.

Adolescent↗
PubMed1994

Selective rubella vaccination programmes: a survey of districts in England and Wales.

A survey of district immunisation coordinators in the 183 health districts of England and Wales was carried out to assess the implementation of selective rubella vaccination programmes. The survey showed that school health services vaccinate schoolgirls against rubella in 161 (93%) of the 173 districts whose immunisation coordinators responded. The accuracy of data on vaccination coverage of schoolgirls is limited because districts interpret the numerator and denominator required by the Department of Health in different ways. Districts have also experienced problems in monitoring the uptake of vaccination through general practitioners. Comprehensive antenatal screening programmes for rubella immunity operate in 164 districts (95%), but few districts are auditing the postpartum vaccination of seronegative women. If child health computer records were maintained and updated until children left school, it would be possible to produce reliable data on the percentage of girls who had been vaccinated against rubella by the age of 14.

Adolescent↗
PubMed1994

Consequences of varicella and herpes zoster in pregnancy: prospective study of 1739 cases.

In a joint prospective study in Germany and the United Kingdom between 1980 and 1993, 1373 women who had varicella and 366 who had herpes zoster during the first 36 weeks of gestation were followed up. 9 cases of congenital varicella syndrome were identified, all occurring after maternal varicella during the first 20 weeks of gestation. The highest risk (2.0%) was observed between 13-20 weeks gestation, with 7 affected infants identified among 351 pregnancies (95% CI of risk 0.8-4.1%). Only 2 cases of congenital varicella syndrome were identified among 472 pregnancies in which maternal varicella occurred before 13 weeks (observed risk 0.4%, 95% CI 0.05-1.5%). Herpes zoster in infancy was reported in 10 children whose mothers had had varicella in pregnancy. No infants with clinical evidence of intrauterine infection were born to the 366 women with herpes zoster in pregnancy (upper 95% confidence limit of estimated risk 1.0%). Varicella-zoster-specific IgM antibody was found at birth in 4 of 16 (25%) infants with clinical manifestations of intrauterine infection and persistent specific IgG antibody in 5 of 7 infants tested. The corresponding rates in asymptomatic infants whose mothers had varicella were 12% (76/615) and 7% (22/335) respectively. No serological evidence of intrauterine infection was found in infants who mothers had herpes zoster in pregnancy. In 97 pregnant women, varicella occurred after post-exposure prophylaxis with anti-varicella-zoster immunoglobulin. No cases of congenital varicella syndrome or zoster in infancy occurred in this group. Our estimates provide a sound basis for counselling women with varicella in pregnancy. Although the risk of congenital varicella syndrome is small, the outcome for the affected infant is so serious that a reliable method of prenatal diagnosis would be valuable. In the long term, prevention of maternal varicella would be an option if a safe and effective vaccine were to become routinely available.

Abortion, Spontaneous↗
PubMed1994

Measles in secondary school children: implications for vaccination policy.

The reported incidence of measles in children of secondary school age rose in 1992, after a progressive decline between 1988 and 1991. This rise was maintained in 1993. Several school and community based outbreaks of measles have occurred in the United Kingdom. This paper reports the investigation of an outbreak of measles based in a secondary school, which took place in 1992. Thirty clinical cases were detected among the school's 840 pupils and 10 sporadic cases occurred outside the school. Twenty-one of the school cases provided samples of serum, in 19 of which measles IgM was detected. The overall attack rate was 3.6%, with no significant differences attributable to age and sex. Vaccine efficacy was about 90%. This outbreak is one of the first to be described in the United Kingdom, although other countries (notably the United States) have reported measles in teenagers. The small degree of spread in the community may reflect the current high uptake of measles, mumps, and rubella vaccine and the catch up campaign that took place in 1988. The feasibility and cost effectiveness of various policy options to prevent future outbreaks in secondary schools are now being evaluated.

Adolescent↗
PubMed1994

Salivary diagnosis of measles: a study of notified cases in the United Kingdom, 1991-3.

OBJECTIVES: To validate a method for salivary diagnosis of measles and to assess the diagnostic accuracy of notified cases of measles. DESIGN: Blood and saliva samples were collected within 90 days of onset of symptoms from patients clinically diagnosed as having measles and tested for specific IgM by antibody capture radioimmunoassay. SETTING: 17 districts in England and one in southern Ireland during August 1991 to February 1993. SUBJECTS: 236 children and adults with measles notified by a general practitioner. RESULTS: Specific IgM was detected in serum in only 85 (36%) of the 236 cases. In cases associated with outbreaks and tested within six weeks of onset, 53/57 (93%) of samples were IgM positive, thereby confirming the sensitivity of serum IgM detection as a marker of recent infection. The serological confirmation rate was lower in cases with a documented history of vaccination (13/87; 15%) than in those without (70/149; 47%) and varied with age, being lowest in patients under a year, of whom only 4/36 (11%) were confirmed. Measles specific IgM was detected in 71/77 (92%) of adequate saliva samples collected from patients with serum positive for IgM. In cases where measles was not confirmed, 6/101 had rubella specific IgM and 5/132 had human parvovirus B19 specific IgM detected in serum. CONCLUSIONS: The existing national surveillance system for measles, which relies on clinically diagnosed cases, lacks the precision required for effective disease control. Saliva is a valid alternative to serum for IgM detection, and salivary diagnosis could play a major role in achieving measles elimination. Rubella and parvovirus B19 seem to be responsible for a minority of incorrectly diagnosed cases of measles in the United Kingdom and other infectious causes of measles-like illness need to be sought.

Adolescent↗
PubMed1994

Pre-eclampsia and serum antibodies to oxidised low-density lipoprotein.

Oxidised low-density lipoprotein (Ox-LDL) has been associated with arterial foam-cell formation, and autoantibodies to Ox-LDL are present in human serum. Lipid peroxidation is enhanced in pre-eclampsia. We assessed whether the titre of IgG autoantibody to an epitope of Ox-LDL, malondialdehyde-conjugated low-density lipoprotein (MDA-LDL), was increased in the sera of pre-eclamptic patients. 16 such patients had significantly higher mean titres of autoantibodies to MDA-LDL than healthy pregnant women (p = 0.028). In a multiple regression model, pre-eclamptic patients still had a significantly higher mean titre (p = 0.048). Enhanced lipid peroxidation may be involved in the foam-cell formation of decidua and in the pathogenesis of pre-eclampsia.

Adult↗