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PubMedDate not supplied

Magnitude of alloresponses to MHC class I/II expressing human cardiac myocytes is limited by their intrinsic ability to process and present antigenic peptides.

In this investigation we have explored the relationship between the weak allogenicity of cardiac myocytes and their capacity to present allo-antigens by examining the ability of a human cardiac myocyte cell line (W-1) to process and present nominal antigens. W-1 cells (HLA-A*0201 and HLA-DR beta1*0301) pulsed with the influenza A matrix 1 (58-66) peptide (M1) were able to serve as targets for the HLA-A*0201 restricted CTL line PG, specific for M1-peptide. However, PG-CTLs were unable to lyse W-1 target cells infected with a recombinant vaccinia virus expressing the M1 protein (M1-VAC). Pretreatment of these M1-VAC targets with IFN-gamma partially restored their ability to process and present the M1 peptide. However, parallel studies demonstrated that IFN-gamma pretreated W-1's could not process tetanus toxin (TT) or present the TT(830-843) peptide to HLA-DR3 restricted TT-primed T cells. Semi-quantitative RT-PCR measurements revealed significantly lower constitutive levels of expression for MHC class I, TAP-1/2, and LMP-2/7 genes in W-1s that could be elevated by pretreatment with IFN-gamma to values equal to or greater than those expressed in EBV-PBLs. However, mRNA levels for the genes encoding MHC class II, Ii, CIITA, and DMA/B were markedly lower in both untreated and IFN-gamma pretreated W-1s relative to EBV-PBLs. Furthermore, pulse-chase analysis of the corresponding genes revealed significantly lower protein levels and longer half-life expression in W-1s relative to EBV-PBLs. These results suggest that weak allogenicity of cardiac myocytes may be governed by their limited expression of MHC genes and gene products critical for antigen processing and presentation.

Amino Acid Sequence↗
PubMed1980

Isolation and partial characterization of the human homologue of Thy-1.

A glycoprotein of 25,000 daltons was isolated from a human T lymphoblastoid cell line (MOLT-3). A monovalent antiserum raised against this antigen precipitated mouse Thy-1.1 antigen as well as a 25,000-dalton antigen from human blood T cells. The unabsorbed serum was also cytotoxic for both mouse and human T cells. By multiple criteria, this human T antigen appears to be homologous with mouse Thy-1.

Animals↗
PubMed2000

Measurement of a Peak in the Cosmic Microwave Background Power Spectrum from the North American Test Flight of Boomerang.

We describe a measurement of the angular power spectrum of anisotropies in the cosmic microwave background (CMB) at scales of 0&fdg;3 to 5 degrees from the North American test flight of the Boomerang experiment. Boomerang is a balloon-borne telescope with a bolometric receiver designed to map CMB anisotropies on a long-duration balloon flight. During a 6 hr test flight of a prototype system in 1997, we mapped more than 200 deg(2) at high Galactic latitudes in two bands centered at 90 and 150 GHz with a resolution of 26&arcmin; and 16&farcm;5 FWHM, respectively. Analysis of the maps gives a power spectrum with a peak at angular scales of 1 degrees with an amplitude 70 µK(CMB).

Journal Article↗
PubMed2000

A Measurement of Omega from the North American Test Flight of Boomerang.

We use the angular power spectrum of the cosmic microwave background, measured during the North American test flight of the Boomerang experiment, to constrain the geometry of the universe. Within the class of cold dark matter models, we find that the overall fractional energy density of the universe Omega is constrained to be 0.85</=Omega</=1.25 at the 68% confidence level. Combined with the COBE measurement, the data on degree scales from the Microwave Anisotropy Telescope in Chile, and the high-redshift supernovae data, we obtain new constraints on the fractional matter density and the cosmological constant.

Journal Article↗
PubMed1999

Correlation of opsonophagocytosis and passive protection assays using human anticapsular antibodies in an infant mouse model of bacteremia for Streptococcus pneumoniae.

An infant mouse assay system for assessment of protective concentrations of human serum pneumococcal anticapsular antibodies is described. Passive immunization of anticapsular antibodies was evaluated for protection of infant mice challenged with Streptococcus pneumoniae serotypes 1, 4, 5, 6B, 18C, and 23A, with bacteremia as an end point. Protection was defined as no detectable bacteremia in 70% of mice 48 h after challenge. Type-specific anticapsular concentrations required for protection varied with serotype (</=0.05 to >0.4 microg/mL). Across serotypes, there was no significant correlation between human IgG concentration in mouse serum and protection from bacteremia or between IgG concentration and opsonophagocytic titer. Significant correlation (r=.84, P<.001) was observed between opsonophagocytic titer of human IgG antibody in mouse sera and protection from bacteremia. Thus, protective concentrations of anticapsular antibodies against bacteremia are serotype dependent. Opsonophagocytosis is a better predictor of in vivo protective capacity of pneumococcal anticapsular antibodies than are ELISA IgG antibody concentrations.

Animals↗
PubMed2002

Inhibition of pneumococcal carriage in mice by subcutaneous immunization with peptides from the common surface protein pneumococcal surface adhesin a.

Pneumococcal surface adhesin A (PsaA), a common protein expressed on all 90 pneumococcal serotypes, is a vaccine candidate. Three anti-PsaA monoclonal antibody phage display-expressed monopeptides (15 mers), in various formulations as lipidated or nonlipidated multiantigenic peptides or as bi- or tripeptide constructs, were studied in a mouse nasopharyngeal carriage model to determine the inhibitory effect of induced antibodies on carriage of pneumococcal serotypes 2, 4, and 6B. Antibodies to each of the various peptides tested reduced carriage of the 3 serotypes. Reduction in carriage by nonlipidated multiantigenic peptide antibodies was highly variable (39%-94%; mean, 59%; standard deviation [SD], 20.2%); however, more-consistent results were observed in mice immunized with lipidated (56%-98%; mean, 69%; SD, 13.6%) and combination or bipeptide (55%-91%; mean, 76%; SD, 13.1%) formulations. These peptides are immunogenic, and their induced antibodies reduce carriage in mice. PsaA peptides demonstrate potential for being important new vaccines against pneumococcal carriage, otitis media, and invasive pneumococcal disease.

Adhesins, Bacterial↗
PubMed2003

Immunizations with pneumococcal surface protein A and pneumolysin are protective against pneumonia in a murine model of pulmonary infection with Streptococcus pneumoniae.

Intranasal infection of mice with certain strains of capsular group 19 Streptococcus pneumoniae can result in focal pneumonia in the absence of bacteremia. Using this model of murine pneumonia, we demonstrated that immunization with recombinant forms of either pneumococcal surface protein A (PspA) or PdB (a genetically detoxified derivative of pneumolysin) elicited significant protection against focal pulmonary infection. This may be the first demonstration that a proposed vaccine antigen can protect against pneumococcal pneumonia. The best protection was obtained by immunizing mice with a mixture of PspA and PdB, indicating that the protection elicited by these antigens can complement each other. This result is in agreement with previous studies that used pneumococcal sepsis and nasal colonization models and demonstrate that the best protein vaccines for prevention of infection may be those that include more than one protection-eliciting pneumococcal protein.

Administration, Intranasal↗
PubMed2000

Selection of an immunogenic and protective epitope of the PsaA protein of Streptococcus pneumoniae using a phage display library.

Streptococcus pneumoniae is an important pathogen that causes disease in young and elderly individuals. The currently available polysaccharide vaccines have limited efficacy in those age groups most susceptible to pneumococcal infections. This study focuses on mapping the epitopes of a surface protein of S. pneumoniae by biopanning a 15 mer phage display library using 5 different monoclonal antibodies (MAbs) against the Pneumoccal surface adhesin A (PsaA). PsaA is a component of the bacterial cell wall that is highly species specific and is involved in bacterial adherence and virulence. Biopanning of the phage display library reveals three distinct epitopes on the PsaA protein. The sequence homology of these epitopes ranges from two to six amino acids when compared to the native PsaA protein type 2. Two of these epitopes have been evaluated for their immunogeneicity in mice. The peptide selected by the MAbs 8G12, 6F6, and 1B7 is referred to as the consensus peptide and is immunogenic in mice. Optimal anti-PsaA response is observed in mice immunized with 50microg of the consensus peptide complexed to proteosomes in 1:1 ratio. The anti-PsaA response is significantly lower than the response to the PsaA native protein. The peptide selected by monoclonal antibody 4E9 in its lipidated form is significantly protective in mice challenged with S. pneumoniae serotype 2 when compared to mice immunized with the native protein. These results show that the selected epitopes of PsaA protein are immunogenic and protective in mice. These epitopes need to be evaluated further as alternatives to currently available vaccines.

Adhesins, Bacterial↗
PubMed1996

Amelioration of the inhibition of fibrinolysis in elderly, obese subjects by moderate energy intake restriction.

A possible cause of accelerated atherothrombosis in the syndrome of insulin resistance appears to be an elevated blood concentration of plasminogen activator inhibitor type-1 (PAI-1). Insulin resistance occurs with aging, attributable partly to increased adiposity. Scarce information exists regarding the effects of weight loss in elderly, obese individuals on PAI-1 concentrations. Consequently, weight loss (9 +/- 1 kg) was induced by energy intake restriction in 19 elderly, obese individuals, and its effect on fibrinolytic system peptides was measured. Initially elevated PAI-1 concentrations decreased by 50%, with a simultaneous decrease in the concentration of tissue-type plasminogen activator (t-PA)/PAI-1 complexes but no significant change in t-PA suggested a decrease in inhibition of the fibrinolytic system. The concentration of plasmin/antiplasmin complexes (PAP complex) increased by approximately 20%, indicating augmented fibrinolytic system activity. The decline in PAI-1 correlated with that of the decrease in body weight (r = 0.5, P < 0.05) and fat mass losses (r = 0.46, P < 0.05). The increase in PAP complexes correlated with weight and fat mass losses (r = 0.4 and r = 0.46, respectively; P < 0.05 for both). No correlation was seen between fibrinolytic system variables and baseline concentrations of substrates or insulin, but the change in PAI-1 correlated with the change in plasma triacylglycerols (r = 0.58, P < 0.05). Results indicate that energy restriction sufficient to induce moderate weight loss leads to diminution of elevated plasma PAI-1 and relief of inhibition of the fibrinolytic system in elderly, obese subjects. To the extent that these changes are associated with a decrease in the progression of vasculopathy, weight loss in elderly, obese individuals may be a useful means to reduce cardiovascular morbidity and mortality.

Aged↗
PubMed1999

Physical activity, protein intake, and appendicular skeletal muscle mass in older men.

BACKGROUND: Aging is associated with physical inactivity, low energy intake, and loss of skeletal muscle mass. It is not clear whether regular physical activity and adequate dietary protein intake can attenuate the loss of skeletal muscle mass. OBJECTIVE: We hypothesized that the maintenance of physical activity and dietary protein intake would attenuate the age-related decline in total appendicular skeletal muscle mass. DESIGN: Total appendicular skeletal muscle mass was determined by dual-energy X-ray absorptiometry in 44 healthy, older white men aged 49-85 y. Physical activity level was determined by using a uniaxial accelerometer over a 9-d period. Dietary protein intake was estimated from a 3-d food record. RESULTS: Aging was inversely associated with total appendicular skeletal muscle mass in older men (r = -0.43; slope: -0. 119 +/- 0.039 kg/y; P < 0.01). An effect of age on appendicular skeletal muscle mass persisted after standing height and physical activity were controlled for (r = -0.34; slope: -0.120 +/- 0.052 kg/y; P = 0.03). Furthermore, an effect of age on appendicular skeletal muscle mass persisted after standing height and dietary protein intake per kilogram body mass was controlled for (r = -0.41; slope: -0.127 +/- 0.045 kg/y; P < 0.01). CONCLUSIONS: Maintaining regular physical activity and adequate protein intake may not offset the age-related loss of appendicular skeletal muscle mass in older men. Prospective studies are needed to confirm these results and to determine whether anabolic physical activity (eg, strength training) can attenuate the age-related loss of muscle mass in the elderly.

Absorptiometry, Photon↗
PubMed1996

Clinical laboratory investigation of the Sanofi ACCESS CK-MB procedure and comparison to electrophoresis and Abbott IMx.

This evaluation was undertaken to verify the application protocol for the CK-MB assay on the ACCESS Immunoassay Analyzer (Sanofi Diagnostics Pasteur, Chaska, MN). The results show that the ACCESS CK-MB assay total imprecision was 6.8% to 9.1%. Analytical linearity of the ACCESS CK-MB assay was excellent in the range of < 1-214 micrograms/L. A comparison of the ACCESS CK-MB assay with the IMx (Abbott Laboratories, Abbott Park, IL) method shows good correlation r = 0.990 (n = 108). Linear regression analysis yielded Y = 1.36X-0.3, Sx/y = 7.2. ACCESS CK-MB values also correlated well with CK-MB by electrophoresis with r = 0.968 (n = 132). The linear regression equation for this comparison was Y = 1.08X + 1.4, Sx/y = 14.1. The expected non-myocardial infarction range of CK-MB determined by the ACCESS system was 1.3-9.4 micrograms/L (mean = 4.0, n = 58). The ACCESS CK-MB assay would appear to be rapid, precise and clinically useful.

Adolescent↗
PubMed1997

CREB is activated by UVC through a p38/HOG-1-dependent protein kinase.

Changes in environmental conditions such as the addition of growth factors or irradiation of cells in culture first affect immediate response genes. We have shown previously that short wavelength UV irradiation (UVC) elicits massive activation of several growth factor receptor-dependent pathways. At the level of the immediate response gene c-fos, these pathways activate the transcription factor complex serum response factor (SRF)-p62TCF which mediates part of the UV-induced transcriptional response. These studies have, however, suggested that more that one pathway is required for full UV responsiveness of c-fos. Using appropriate promoter mutations and dominant-negative cAMP response element (CRE)-binding protein (CREB), we now find that UVC-induced transcriptional activation depends also on the CRE at position -60 of the c-fos promoter and on the functionality of a CREB. Upon UV irradiation, CREB and ATF-1 are phosphorylated at serines 133 and 63, respectively, preceded by and dependent on activation of p38/RK/HOG-1 and of a p38/RK/HOG-1-dependent p108 CREB kinase. Although p90RSK1 and MAPKAP kinase 2 are also activated by UV, p90RSK1 does not, at least not decisively, participate in this signalling pathway to CREB and ATF-1 as it is not p38/RK/HOG-1 dependent, and CREB is a poor substrate for MAPKAP kinase 2 in vitro. On the basis of resistance to the growth factor receptor inhibitor suramin and of several types of cross-refractoriness experiments, the UVC-induced CREB/ATF-1 phosphorylation represents an as yet unrecognized route of UVC-induced signal transduction, independent of suramin-inhibitable growth factor receptors and different from the Erk 1,2-p62TCF pathway.

Activating Transcription Factor 1↗
PubMed1995

A controlled trial of exercise training in older coronary patients.

BACKGROUND: This study compared the effects of a formal exercise conditioning program of 3 and 12 months duration to spontaneous recovery in a population of older, post-coronary event patients. METHODS: Indices of peak exercise and submaximal exercise performance such as oxygen consumption, treadmill work capacity, minute ventilation, heart rate, and systolic blood pressure were assessed before and after conditioning in 60 post-myocardial infarction and post-coronary bypass surgery patients (mean age 68 +/- 5 years) and compared to measures of fitness in a usual care control group (n = 23, mean age 68 +/- 5 years). RESULTS: Maximal treadmill work capacity increased by 47% in the intervention group at 3 months compared to no improvement in the usual care control group. However, both groups increased peak oxygen consumption similarly at 3 and 12 months, increasing by 16% and 20% in the intervention group at 3 and 12 months and by 7% and 14% in the control group (p = n.s.). Only the exercise training group manifested submaximal indices of conditioning such as a lower heart rate and minute ventilation at a standard workload. CONCLUSION: While spontaneous improvements in peak oxygen consumption are seen in older coronary patients in the months following a coronary event, a formal exercise training program results in significantly greater increases in peak exercise capacity and in peak and submaximal exercise efficiency.

Aged↗
PubMed1998

A review of hepatitis C virus (HCV) vertical transmission: risks of transmission to infants born to mothers with and without HCV viraemia or human immunodeficiency virus infection.

BACKGROUND: Hepatitis C virus (HCV) vertical transmission studies have reported conflicting findings, possibly due to differences in HCV transmission risk factors among maternal populations, or to methodological differences. METHODS: Systematic review of worldwide published and unpublished HCV vertical transmission studies. Standardized diagnostic criteria were applied to minimize methodological differences, and transmission rates recalculated according to maternal HCV viraemic and human immunodeficiency virus (HIV) infection status. RESULTS: In all, 976 eligible infants from 28 studies were followed up sufficiently for recalculation of transmission rates. Overall transmission rates were less than 10% in 8/12 studies of HIV negative mothers, compared with 2/7 studies comprising at least 50% HIV-coinfected mothers. Rates from 409 viraemic mothers in 15 studies ranged from 0% to 41%, being less than 10% from HIV negative mothers in 6/13 studies and from HIV positive mothers in 1/6 studies. Nine studies measured maternal viraemia levels, with only 2/30 transmitting mothers having < 10(6) copies/ml of HCV RNA. Eight transmissions were identified overall from non-viraemic mothers. Significant transmission rate variation remained after accounting for maternal viraemia and HIV coinfection, possibly due to differences in other vertical transmission risk factors, in frequencies of postnatal transmission, or residual differences in study methodologies. CONCLUSIONS: Overall, HCV transmission is largely restricted to infants born to HCV viraemic mothers, and low risks among most HIV negative mothers may be due to lower HCV viraemia levels. International agreement on standardized diagnostic criteria for HCV vertical transmission would facilitate pooling of individual findings, to allow more precise transmission estimates and further investigation of risk factors.

Adult↗
PubMed2000

The public health applications of unlinked anonymous seroprevalence monitoring for HIV in the United Kingdom.

BACKGROUND: In order to monitor the epidemiology of human immunodeficiency virus (HIV), integrated national programmes of unlinked anonymous (blinded) HIV sero-surveys have taken place in the UK since 1990. METHODS: The programmes comprise multi-centre surveys primarily using specimens gathered routinely for screening groups of patients. All specimens are irreversibly unlinked from patient identifiers before being tested. RESULTS: The surveys have met their prime aim of providing at low cost minimally biased estimates of current HIV prevalence and trends in sentinel populations. The surveys have remained acceptable to professionals and the public, being successfully implemented without breech of their founding principles. The findings have had major public health applications, have influenced HIV policy and funding, been used for monitoring the spread of HIV, for targeting and evaluating health promotion and improving projections of severe HIV disease. The surveys have detected substantial prevalence rises and under-diagnosis of HIV which would otherwise have been unrecognised. The programmes' value is being increased by sub-typing HIV-1 isolates, capturing additional demographic information to detect spread among minority groups. The same specimens are used for monitoring other infections (initially hepatitis A, B and C). CONCLUSIONS: Monitoring HIV and other infections through unlinked anonymous HIV surveillance has become an integral essential part of national HIV and AIDS surveillance. Although it has unique applications the value of unlinked anonymous surveillance is maximized when used in conjunction with behavioural data, information from HIV and AIDS reporting, and behavioural data and surveillance for other sexually transmitted infections.

Confidentiality↗
PubMed2001

Effect of prenatal treatment on mother to child transmission of Toxoplasma gondii: retrospective cohort study of 554 mother-child pairs in Lyon, France.

BACKGROUND: The aim of prenatal serological screening for toxoplasmosis is to identify and treat maternal infection as soon as possible in order to prevent transmission of the parasite to the fetus. However, despite widespread provision of prenatal toxoplasma screening across Europe, the effectiveness of prenatal treatment is uncertain. The study aimed to determine the effect of the timing and type of prenatal treatment on mother to child transmission of Toxoplasma gondii. METHOD: A cohort of 554 infected pregnant women were identified in Lyon, France between 1987 and 1995 and their children were followed to determine congenital infection status. We determined the effect of prenatal treatment on transmission by examining the effect of the delay between maternal seroconversion and start of treatment. We also compared the effect of the type of treatment and no treatment on the risk of mother to child transmission. Analyses were adjusted for gestation at maternal seroconversion. RESULTS: Compared to treatment within 4 weeks from seroconversion, the adjusted odds ratios (OR) for mother to child transmission after a treatment delay of 4-7 weeks was 1.29 (95% CI : 0.61, 2.73) and after more than 8 weeks, 1.44 (95% CI : 0.60, 3.31). The adjusted OR associated with spiramycin alone compared with pyrimethamine-sulfadiazine treatment was 0.91 (95% CI : 0.45, 1.84) and the OR for no treatment compared with pyrimethamine-sulfadiazine treatment was 1.06 (95% CI : 0.37, 3.03). CONCLUSIONS: The authors hypothesize that the absence of an effect of prenatal treatment is due to transmission before the start of treatment.

Adult↗