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PubMed1996

Glycoproteins E2 of the Venezuelan and eastern equine encephalomyelitis viruses contain multiple cross-reactive epitopes.

Enzyme immunoassay (EIA) with sixty types of monoclonal antibodies (MAbs) was used to study cross-reactive epitopes on the attenuated and virulent strains of the Eastern equine encephalomyelitis (EEE) and Venezuelan equine encephalomyelitis (VEE) viruses. All three structural proteins of the EEE and VEE viruses were demonstrated to have both cross-reactive and specific antigenic determinants. The glycoprotein E1 of EEE and VEE viruses possesses three cross-reactive epitopes for binding to MAbs. The glycoprotein E2 has a cluster of epitopes for 20 cross-reacting MAbs produced to EEE and VEE viruses. Cross-reactive epitopes were localised within five different sites of glycoprotein E2 of VEE virus and within four sites of that of the EEE virus. There are no cross-neutralising MAbs to the VEE and EEE viruses. Only one type of the protective Mabs was able to cross-protect mice against lethal infection by the virulent strains of the VEE and EEE viruses. Eight MAbs blocked the hemagglutination activity (HA) of both viruses. Antigenic alterations of neutralising and protective sites were revealed for all attenuated strains of the VEE and EEE viruses. Comparative studies of the E2 proteins amino acid sequences show that the antigenic modifications observed with the attenuated strains of the VEE virus may be caused by multiple amino acid changes in positions 7, 62, 120, 192 and 209-213. The escape-variants of the VEE virus obtained with cross-reactive MAbs 7D1, 2D4 and 7A6 have mutations of the E2 protein at positions 59, 212-213 and 232, respectively. Amino acid sequences in these regions of the VEE and EEE viruses are not homologous. These observations indicate that cross-reactive MAbs are capable of recognising discontinuous epitopes on the E2 glycoprotein.

Amino Acid Sequence↗
PubMed1983

Effects of pretreatment with coenzyme Q10 on myocardial preservation during aortic cross clamping.

A protective effect of coenzyme Q10 on the ischemic and reperfused myocardium was investigated in the isolated working rat heart preparation. Rats were treated intraperitoneally with 30 mg/kg coenzyme Q10, daily for 7 days. The controls were given the same dose of the vehicle. After 25 min of equilibration the hearts were made totally ischemic at 35.5 degrees C for 30 min, arrested with high potassium cardioplegic solution immediately after aortic cross clamping. The recovery of cardiac power in the coenzyme Q10 pretreated group was significantly (P less than 0.05) better than that in vehicle pretreated group. Creatine phosphokinase (CPK) release during reperfusion was significantly (P less than 0.05) reduced by the pretreatment of coenzyme Q10. Tissue analysis for high energy phosphate compounds revealed no significant difference between the two groups. Tissue lactate content at 30 min of ischemia was significantly (P less than 0.001) lower in the coenzyme Q10 pretreated group. These results suggest that pretreatment with coenzyme Q10 is effective for reducing ischemic injury caused by aortic cross clamping.

Animals↗
PubMed1989

Contralateral cochlear destruction mediates protection from monoaural loud sound exposures through the crossed olivocochlear bundle.

Destruction of the cochlea contralateral to one subsequently exposed to a high intensity acoustic exposure has been shown to reduce the threshold losses caused by the exposure (Rajan and Johnstone, 1983a). The present study tested this manipulation on a wide variety of exposures of varying intensity and duration and found that the amount by which ipsilateral threshold losses were reduced was related to the amount of threshold losses that would have occurred in the absence of the contralateral manipulation. This loss-related protection is also found when the COCB is electrically stimulated during loud sound exposures (Rajan, 1988b; Rajan and Johnstone, 1988b). When the COCB was lesioned at the floor of the fourth ventricle contralateral cochlea destruction no longer protected the test cochlea, confirming that the crossed cochlear protection was exercised through the COCB. The contralateral manipulation did not appear to directly activate the COCB but may have acted in a facilitatory manner on the COCB, allowing activation only when a sufficiently high level exposure was subsequently presented ipsilaterally: a variety of responses at the ipsilateral cochlea and at the brainstem, remeasured after contralateral cochlear destruction and prior to an ipsilateral loud sound exposure, were found to be unaltered, although the TTS to the subsequent exposure was significantly reduced.

Animals↗
PubMed2001

A novel liposomal influenza vaccine (INFLUSOME-VAC) containing hemagglutinin-neuraminidase and IL-2 or GM-CSF induces protective anti-neuraminidase antibodies cross-reacting with a wide spectrum of influenza A viral strains.

A liposomal influenza vaccine (INFLUSOME-VAC) was developed with the objective of overcoming the major drawbacks of the currently used influenza vaccines: their relatively low efficacy in certain high-risk groups (the elderly, infants, the immunosuppressed) and the need for annual immunization. INFLUSOME-VAC consists of liposomes containing the viral surface proteins hemagglutinin (HA) and neuraminidase (NA) derived from various influenza strains and IL-2 or GM-CSF, as an adjuvant. Vaccination of mice showed that, whereas conventional vaccines induced a low- and short-term response against HA and very low or no anti-NA response, INFLUSOME-VAC produced high titers of both anti-HA and anti-NA antibodies (Abs) in young and old mice that persisted for at least 6 months. Moreover, the anti-NA Abs efficiently cross-reacted with several N2 viral subtypes spanning 20 years, and such vaccines afforded partial protection against heterosubtypic viral infection.

Animals↗
PubMed2001

Synthesis and characterization of DNA duplexes containing an N(4)C-ethyl-N(4)C interstrand cross-link.

Short DNA duplexes containing an N(4)C-ethyl-N(4)C interstrand cross-link, C-C, were synthesized on controlled pore glass supports. Duplexes having two, three, or four A/T base pairs on either side of the C-C cross-link and terminating with a C(4) overhang at their 5'-ends were prepared. The cross-link was introduced using a convertible nucleoside approach. Thus, an oligonucleotide terminating at its 5'-end with O(4)-triazoyl-2'-deoxyuridine was first prepared on the support. The triazole group of support-bound oligomer was displaced by the aminoethyl group of 5'-dimethoxytrityl-3'-O-tert-butyldimethylsilyl-N(4)-(2-aminoethyl)deoxycytidine to give the cross-link. The dimethoxytrityl group was removed, and the upper and lower strands of the duplex were extended from two 5'-hydroxyl groups of the cross-link using protected nucleoside 3'-phosphoramidites. The tert-butyldimethylsilyl group of the resulting partial duplex was then removed, and the chain was extended in the 3'-direction from the resulting 3'-hydroxyl of the cross-link using protected nucleoside 5'-phosphoramidites. The cross-linked duplexes were purified by HPLC and characterized by enzymatic digestion and MALDI-TOF mass spectrometry. Duplexes with three or four A/T base pairs on either side of the C-C cross-link gave sigmoidal shaped A(260) profiles when heated, a behavior consistent with cooperative denaturation of the A/T base pairs. Each cross-linked duplex could be ligated to an acceptor duplex using T4 DNA ligase, a result that suggests that the C-C cross-link does not interfere with the ligation reaction, even when it is located only two base pairs from the site of ligation. The ability to synthesize duplexes with a defined interstrand cross-link and to incorporate these duplexes into longer pieces of DNA should enable preparation of substrates that can be used for a variety of biophysical and biochemical experiments, including studies of DNA repair.

Cross-Linking Reagents↗
PubMed2004

A cross-national comparison of risk and protective factors for adolescent substance use: the United States and Australia.

PURPOSE: To compare risk and protective factors that influence youth substance use in Australia and the United States. The two countries have different policy orientations toward substance use: Australia has adopted harm-reduction policies, and the United States has adopted abstinence-focused policies. METHODS: Cross-sectional survey data were collected from independent samples of adolescents in the states of Maine (N = 16,861; 53% female, 7% Non-white) and Oregon (N = 15,542; 51% female, 24% Non-white) in the United States and Victoria in Australia (N = 8442; 54% Female, 11% Non-white) in 1998 (Maine and Oregon) and 1999 (Victoria). Chi-square tests, t-tests, effect size comparisons, and logistic regression analyses that accounted for age and gender were used to investigate cross-national similarities and differences in: (a) rates of cigarette, alcohol, and marijuana use; (b) levels of risk and protective factors; and (c) magnitudes of associations between risk and protective factors and substance use. RESULTS: More adolescents in Victoria reported using cigarettes and alcohol, whereas more of the U.S. adolescents reported using marijuana. Exposure to risk and protective factors was generally similar in the cross-national samples. However, adolescents in Maine and Oregon perceived handguns to be more readily available, reported more participation in religious activities, and were higher in sensation-seeking and social skills; and adolescents in Victoria had more favorable attitudes toward drug use and reported community norms and parental attitudes more favorable to drug use. Most of the risk and protective factors were strongly associated with substance use to a similar degree in Victoria, Maine, and Oregon. However, among adolescents in Maine and Oregon peer/individual risk and protective factors associated with social detachment were more strongly related to substance use, and among adolescents in Victoria, family protective factors were less strongly related to alcohol use. CONCLUSIONS: Inter-country influences on youth substance use are generally similar despite different policy directions. Existing differences suggest that the abstinence policy context is associated with higher levels of illicit drug use and stronger relations between individual indicators of social detachment and substance use, whereas the harm reduction policy context is related to more cigarette and alcohol use, possibly from exposure to normative influences that are more tolerant of youth drug use.

Adolescent↗
PubMed1968

Cross-reactions among Group A streptococci. I. Precipitin and bactericidal cross-reactions among types 33, 41, 43, 52, and Ross.

Strains of four streptococcal types, 33, 41, 43, 52, and a nontypable strain, Ross, cross-reacted in precipitin and bactericidal tests. The homologous reactions, which determined the type, afforded the major protection and developed promptly and regularly in the serum of rabbits during immunization. The associated cross-reactions, on the other hand, appeared in the serum of certain rabbits only, were often not as strong as the associated homologous reactions, and required for their presence a longer period of immunization than the homologous reactions. Agar gel analysis of the homologous precipitin reactions revealed, as would be expected, reactions of serological identity, while those cross-reactions which were strong enough to test in this way formed bands of precipitate which joined with spur formation on the side of the homologous reaction. These experiments and others referred to in the text suggest that cross-protection, as demonstrated in bactericidal tests, is sufficiently widespread to be a factor in streptococcal immunity, if a corresponding protection occurs in vivo. Thus, streptococcal infection with one of the cross-reacting strains might confer, in addition to strong homologous protection, a certain amount of cross-protection.

Agglutination Tests↗
PubMed2005

Relational factors of vulnerability and protection for adolescent pregnancy: a cross-sectional comparative study of Portuguese pregnant and nonpregnant adolescents of low socioeconomic status.

This study explores multiple relational contexts that promote vulnerability and protection against early pregnancy in a potential risk group of Portuguese adolescents. A comparative analysis was made between two groups of female adolescents of low socioeconomic status: pregnant adolescents (n=57) and adolescents without a history of pregnancy (n=81). Results suggest that several variables belonging to different contexts-family and school and peer relations--are important in the characterization of the two groups. Lower levels of mother's overprotection and father's emotional support, presence of early pregnancy in adolescent's mother, lower level of emotional proximity to peer relations, and higher number of school failures are significantly associated with adolescent pregnancy.

Adolescent↗
PubMedDate not supplied

[Comparative effects of bamifylline and theophylline on allergenic bronchospasm induced by the provocative inhalation test : double-blind cross-over study].

Protective and curative effects of parenterally administered bamifylline and theophylline on bronchospasm induced by standardized house dust inhalation were studied in two series of eight patients with allergic asthma to house dust. Preventive effects were assessed by variations in liminal allergen dose (LAD) required to double resistance of the air passages (Rap), measured by barometric body plethysmography after determining basal LAD levels. Thirty minutes afer a slow i.v. injection of bamifylline, and LAD mean value reached 920 +/- 950 % of control value, and was still at 830 +/- 1 000 % after 60 minutes. After theophylline, mean LAD values were 750 +/- 980 % at 30 minutes and 700 +/- 970 % at 60 minutes, a non-significant difference. Curative activity was evaluated by studying changes in Rap after the provocative inhalation test with house dust, the test being immediately followed by the administration of either bamifylline or theophylline. Similar results were also obtained employing this test : reduction in Rap of 35 +/- 17 % for bamifylline and 48 +/- 13 % for theophylline (non-significant difference) after 30 minutes, and of 38 +/- 25 % for bamifylline and 48 +/- 14 % for theophylline (non-significant difference) after 60 minutes. These findings suggest that these two xanthine derivatives possess comparable protective and curative effects against bronchospasm induced by allergen inhalation.

Adult↗
PubMed1983

Heterologous immunity in rodent malaria: comparison of the degree of cross-immunity generated by vaccination with that produced by exposure to live infection.

The degree of heterologous immunity occurring between the different rodent malarias was examined. Mice immunized with a killed vaccine consisting of formalin-fixed blood-stage parasites mixed with saponin, were challenged with homologous or heterologous parasites and the degree of protection assessed by monitoring the number of survivors and the duration and severity of parasitaemia. The results indicated that vaccination conferred strong cross-protection between two different Plasmodium yoelii lines and also some cross-protection between different species. The most significant inter-species cross-immunity was in P. berghei-vaccinated mice challenged with P. yoelii (33% survival rate) and in P. vinckei-vaccinated mice challenged with P. chabaudi (50% survival rate). The protection operated only in one direction since mice vaccinated against P. yoelii or P. chabaudi were fully susceptible to P. berghei and P. vinckei respectively, although extension of the survival time did occur in both cases. Significantly greater levels of homologous and heterologous immunity occurred in vaccinated mice which had cleared a primary homologous infection. All recovered animals were fully resistant to homologous secondary challenges. P. berghei-recovered mice had complete resistance to a secondary P. yoelii challenge, with partial resistance also to P. vinckei and P. chabaudi: P. vinckei-recovered mice were completely resistant to P. chabaudi challenge and showed partial resistance to P. berghei (50% survival rate). Conversely, no reduction in mortality occurred in P. chabaudi-recovered mice challenged with any heterologous parasite. Plasmodium yoelii-recovered animals were fully susceptible to P. vinckei but showed some resistance to P. berghei and P. chabaudi (33 and 17% survival respectively). Many lesser instances of cross-resistance were observed in the present study and are discussed in the text but they were not sufficiently powerful to reduce mortality. The present study provides the first reported comprehensive investigation on cross-resistance in rodent malarias generated by a killed vaccine. In addition this is the only complete cross-resistance study available which has concentrated exclusively upon highly lethal strains of each parasite species. Taken with the rechallenge experiments, the results extend, and to a certain point confirm, previous observations on cross-immunity in the rodent malarias. However, several of the present results conflict with previous reports and these are discussed in relation to the relevant literature.

Animals↗
PubMed1988

Hymenolepis muris-sylvaticae and H. microstoma: immunological cross-reaction in mice.

A primary infection with Hymenolepis microstoma strongly protects against cross-infection with H. muris-sylvaticae and also against secondary infection with H. microstoma in NMRI mice, resulting in an accelerated loss of worms and a weight reduction of the remaining worms. A primary infection with H. muris-sylvaticae causes an accelerated rejection of secondary infection with H. muris-sylvaticae but it has no effect on cross-infection with H. microstoma, neither with regard to worm recovery nor with regard to worm biomass. Determinations by enzyme-linked immunosorbent assay of antibody concentrations in the mouse sera revealed that: (1) the antibody response evoked by H. microstoma infection is much greater than by H. muris-sylvaticae infection; (2) a cross-infection with H. muris-sylvaticae boosts the antibody response evoked by H. microstoma infection; (3) H. microstoma antigen can be used to measure antibody concentration against both H. microstoma and H. muris-sylvaticae; and (4) although H. muris-sylvaticae is rejected faster in a cross-infection (i.e., after a primary H. microstoma infection) than in a secondary infection (i.e., after a primary H. muris-sylvaticae infection), antibodies evoked by the primary H. microstoma infection show little cross-reaction with H. muris-sylvaticae antigen. This suggests that it is doubtful whether serum antibodies are the direct effectors in worm rejection.

Animals↗
PubMed1998

Neutron, proton, and photonuclear cross-sections for radiation therapy and radiation protection.

I review recent work at Los Alamos undertaken to evaluate neutron, proton, and photonuclear cross-sections up to 150 MeV (to 250 MeV for protons), based on experimental data and nuclear model calculations. These data are represented in the ENDF format and can be used in computer codes to simulate radiation transport. They permit calculations of absorbed dose in the body from therapy beams, and through use of kerma coefficients allow absorbed dose to be estimated for a given neutron energy distribution. In radiation protection, these data can be used to determine shielding requirements in accelerator environments and to calculate neutron, proton, gamma-ray, and radionuclide production. Illustrative comparisons of the evaluated cross-section and kerma coefficient data with measurements are given.

Carbon↗
PubMed1999

Regulation of monocyte survival in vitro by deposited IgG: role of macrophage colony-stimulating factor.

IgG deposition at tissue sites characteristically leads to macrophage accumulation and organ injury. Although the mechanism by which deposited IgG induces tissue injury is not known, we have recently demonstrated that deposited IgG stimulates the release of IL-8 and monocyte chemoattractant protein-1 from normal human monocytes, which may drive inflammation. Since IgG also induces macrophage accumulation in these diseases, we hypothesized that deposited IgG protects monocytes from apoptosis. As an in vitro model of the effect of deposited IgG on monocyte survival, monocyte apoptosis was studied after FcgammaR cross-linking. Monocytes cultured on immobilized IgG, which induces FcgammaR cross-linking, were protected from apoptosis, whereas monocytes cultured with equivalent concentrations of F(ab')2 IgG or 50 times higher concentrations of soluble IgG, neither of which induces FcgammaR cross-linking, were not protected. Moreover, this protection was transferable, as supernatants from immobilized IgG-stimulated monocytes protected freshly isolated monocytes from apoptosis and contained functional M-CSF, a known monocyte survival factor. M-CSF mediated the monocyte survival induced by FcgammaR cross-linking, as neutralizing anti-human M-CSF Abs blocked the monocyte protection provided by either immobilized IgG or IgG-stimulated monocyte supernatants. These findings demonstrate a novel mechanism by which deposited IgG targets tissue macrophage accumulation through FcgammaR-mediated M-CSF release. This pathway may play an important role in promoting and potentiating IgG-mediated tissue injury.

Antigen-Antibody Complex↗
PubMed2005

Desferrioxamine inhibits production of cytotoxic heme to protein cross-linked myoglobin: a mechanism to protect against oxidative stress without iron chelation.

The heme group of myoglobin can form a covalent bond to the protein when met (ferric) myoglobin is reacted with peroxides under acidic conditions. This heme to protein cross-linked species is highly pro-oxidant and found in the urine of patients with rhabdomyolytic-associated acute renal failure. Desferrioxamine, an iron-chelating agent used in the treatment of iron overload, is reported to be partially effective at preventing kidney failure following rhabdomyolysis. In this article, we show that in addition to its capacity as an iron chelator, desferroxamine can inhibit the peroxide-induced formation of heme to protein cross-linked myoglobin and decreases the pro-oxidant activity of both native and heme to protein cross-linked myoglobin. The mechanism of peroxidation and of heme to protein cross-linking involves the formation of ferryl intermediate (Fe(4+)=O(2-)), and it is by the reduction of this intermediate to the ferric form that desferrioxamine can exert inhibitory effects. The concentrations at which desferrioxamine inhibits the formation of heme to protein cross-linked myoglobin and prevents the pro-oxidant activity of native and oxidatively modified myoglobins are comparable to the concentrations used for in vivo studies of iron-related oxidative stress. Thus, the ameliorative effects of treatment of posthemolytic events by desferrioxamine cannot be exclusively assigned to its ability to chelate free iron.

Animals↗
PubMed1991

Relation of human serum antibody against Staphylococcus epidermidis cell surface polysaccharide detected by enzyme-linked immunosorbent assay to passive protection in the mouse.

A specific and rapid enzyme-linked immunosorbent assay (ELISA) has been applied for the detection of immunoglobulins to Staphylococcus epidermidis cell surface polysaccharides in human serum. Positive IgG, IgM and IgA titres of more than 1: 6400, 1: 1600 and 1: 400 were observed with this assay against passive protective human serum. However, IgG, IgM and IgA titres of less than 1: 400, 1: 100 and 1: 50 were shown in non-protective serum. When the cross-reactivity of passive protective human serum to homologous and heterologous cell surface polysaccharides was examined by inhibition test with ELISA, remarkable inhibition was shown with homologous cell surface polysaccharide, whereas no inhibition was observed with heterologous substances. According to these results, the quantitation of human serum antibody by the ELISA method against Staph. epidermidis cell surface polysaccharide was found to be significant for the demonstration of passive protective activities against Staph. epidermidis.

Animals↗