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At least 1,261 records · Page 70Linked to original sources
PubMed1998

XRCC2 and XRCC3, new human Rad51-family members, promote chromosome stability and protect against DNA cross-links and other damages.

The phenotypically similar hamster mutants irs1 and irs1SF exhibit high spontaneous chromosome instability and broad-spectrum mutagen sensitivity, including extreme sensitivity to DNA cross-linking agents. The human XRCC2 and XRCC3 genes, which functionally complement irs1 and irs1SF, respectively, were previously mapped in somatic cell hybrids. Characterization of these genes and sequence alignments reveal that XRCC2 and XRCC3 are members of an emerging family of Rad51-related proteins that likely participate in homologous recombination to maintain chromosome stability and repair DNA damage. XRCC3 is shown to interact directly with HsRad51, and like Rad55 and Rad57 in yeast, may cooperate with HsRad51 during recombinational repair. Analysis of the XRCC2 mutation in irs1 implies that XRCC2's function is not essential for viability in cultured hamster cells.

Animals↗
PubMed1996

Enoximone usage for experimental spinal cord protection during aortic cross-clamping.

Spinal cord preservation during aortic cross-clamping is of vital importance. Maintenance of spinal cord blood supply is one of the key points for spinal cord preservation. In this study enoximone was selected as an agent to reduce the risk of spinal cord injury because of its inotropic and vasodilator actions. Ten dogs underwent sixty minutes aortic occlusion. Five animals received enoximone and the others did not (the control group). Enoximone dosage was 10 microgram/kg/min. Four dogs in the control group suffered paraplegia. There were no paraplegic events in the enoximone group. Cerebrospinal fluid pressure was 17 +/- 3 mmHg in the control group, 15 +/- 4 mmHg in the enoxirmone group. Distal aortic pressure was 15 +/- 4 mmHg in the control group, 47 +/- 6 in the enoximone group (p < 0.001). In this study we conclude that enoximone is an effective agent to reduce the risk of spinal cord injury.

Animals↗
PubMed1983

Improved myocardial protection during a prolonged cross-clamp period.

Severe coronary stenoses limit delivery of cardioplegic solution to ischemic regions in patients undergoing bypass operations. A prospective randomized trial was undertaken to determine whether the construction of proximal as well as distal anastomoses during a prolonged cross-clamp period would provide more uniform cardiac cooling and better myocardial protection. Ninety-one consecutive patients undergoing elective coronary bypass operations were randomized into two groups. The long cross-clamp technique was used in 46 patients (Group 1), and a proximal anastomosis was constructed after each distal anastomosis. The short cross-clamp technique was employed in 45 patients (Group 2), and distal anastomoses were constructed during aortic occlusion. Cardiopulmonary bypass time was identical, but the cross-clamp period was longer in Group 1 (59 +/- 15 minutes versus 46 +/- 17 minutes in Group 2; p less than 0.001). The mean temperature in the most ischemic region was colder with the long cross-clamp technique (12.5 +/- 3.1 degrees C in Group 1 versus 14.8 +/- 3.2 degrees C in Group 2; p less than 0.01). The total amount of the myocardial isoenzyme of serum creatine kinase released was greater in Group 2 than in Group 1 (332 +/- 34 IU/L per hour in Group 1 versus 469 +/- 45 IU/L per hour in Group 2). Thirty-six patients had coronary sinus catheters inserted (18 patients in each group). Myocardial lactate extraction returned to normal sooner in the patients who had a long cross-clamp period; time to a normal lactate extraction was 0.8 +/- 0.8 hours in Group 1 versus 2.2 +/- 2.1 hours in Group 2 (p less than 0.001). Volume loading and atrial pacing 2 to 4 hours postoperatively produced a similar hemodynamic response in the two groups, but myocardial lactate extraction increased in Group 1 and decreased in Group 2 (p less than 0.05). The construction of proximal as well as distal anastomoses during a prolonged cross-clamp period produced more uniform cooling and improved myocardial protection.

Constriction↗
PubMed1989

Epidemiological models with age structure, proportionate mixing, and cross-immunity.

Infection by one strain of influenza type A provides some protection (cross-immunity) against infection by a related strain. It is important to determine how this influences the observed co-circulation of comparatively minor variants of the H1N1 and H3N2 subtypes. To this end, we formulate discrete and continuous time models with two viral strains, cross-immunity, age structure, and infectious disease dynamics. Simulation and analysis of models with cross-immunity indicate that sustained oscillations cannot be maintained by age-specific infection activity level rates when the mortality rate is constant; but are possible if mortalities are age-specific, even if activity levels are independent of age. Sustained oscillations do not seem possible for a single-strain model, even in the presence of age-specific mortalities; and thus it is suggested that the interplay between cross-immunity and age-specific mortalities may underlie observed oscillations.

Aging↗
PubMed2006

Protective efficacy of a targeted anti-caries DNA plasmid against cariogenic bacteria infections.

We have previously reported that a targeted anti-caries DNA plasmid pGJA-P/VAX which was constructed against the antigenic determinants of Streptococcus mutans (S. mutans) successfully induced antibody responses in mice and monkeys. The present study explored the protective efficacy of pGJA-P/VAX against cariogenic bacterial challenge. Groups of rats were orally challenged with S. mutans or Streptococcus sobrinus (S. sobrinus) and then immunized with pGJA-P/VAX or the vector pVAX1 intranasally. Serum IgG and salivary IgA antibody levels were assessed by an enzyme-linked immunosorbent assay and caries activity was evaluated by the Keyes method. The results showed that specific salivary IgA antibody responses were induced following intranasal vaccination with pGJA-P/VAX. Moreover, immunization with pGJA-P/VAX resulted in significantly reduced enamel and dentinal caries lesions in rats after S. mutans infection and significantly reduced enamel caries lesions after S. sobrinus infection. Thus, pGJA-P/VAX was not only protective toward S. mutans infection, but also provided cross-strain protection against S. sobrinus infection in rats.

Administration, Intranasal↗
PubMed2002

Cross-linked matrix tissue sealant protects against mortality and hemorrhage in an acute renal injury model in heparinized rats.

PURPOSE: We evaluated the efficacy of a cross-linked matrix tissue sealant compared with oxidized cellulose and electrocautery in an acute renal injury model. MATERIALS AND METHODS: Sprague-Dawley rats underwent partial nephrectomy after intravenous heparin anticoagulation. The cut surface received 1 of 4 therapies, namely no treatment, cross-linked matrix tissue sealant, electrocautery or Surgicel (Johnson & Johnson, New Brunswick, New Jersey) oxidized cellulose. Blood pressure was continually monitored, survival time was determined and total blood loss was quantified in each animal. RESULTS: Animals that received no treatment, electrocautery or oxidized cellulose died within 13 minutes of injury with a decline in blood pressure to 0 mm. Hg. In cross-linked matrix treated rats hemostasis was immediate, resulting in no blood loss after cross-linked matrix application. Mean arterial pressure +/- SEM was maintained at 136 +/- 6 mm. Hg. All cross-linked matrix treated animals survived. CONCLUSIONS: Cross-linked matrix tissue sealant provided immediate hemostasis and protection from a decline in blood pressure after renal trauma in heparinized rats. Cross-linked matrix tissue sealant may benefit patients with severe renal injuries. In the future cross-linked matrix may be useful for long-term partial nephrectomy repair.

Animals↗
PubMed1993

Characterization of vascular postsynaptic neuropeptide Y receptor function and regulation. 1. NPY-induced constriction in isolated rat femoral artery rings is mediated by both Y1 and Y2 receptors: evidence from benextramine protection studies.

Neuropeptide Y (NPY), a potent pressor agent and vasoconstrictor, is thought to contribute to the sympathetically mediated postsynaptic regulation of blood pressure primarily through activation of vascular Y1 rather than Y2 NPY receptors. However, data are available that conflict with this conclusion. In this article, the relative roles of postsynaptic Y1 and Y2 receptors as mediators of direct NPY-induced isolated rat femoral artery ring vasoconstriction were evaluated through use of selective Y1 and Y2 agonists, [Leu31, Pro34]NPY ([Leu, Pro]NPY) and NPY13-36 [NPY(13-36)], respectively, and the NPY receptor antagonist benextramine (BXT). NPY, [Leu, Pro]NPY and NPY(13-36) were equipotent as vasoconstrictors, and constriction induced by each peptide, but not by the calcium channel agonist BAY K 8644 (BAY), was almost completely blocked by 10 microM BXT. Each of the three peptides also induced self- and cross-desensitization and protection from BXT blockade, except that [Leu, Pro]NPY neither desensitized nor protected NPY(13-36)-associated responses. NPY also failed to protect [Leu, Pro]NPY- and NPY(13-36)-elicited constriction, and NPY(13-36) failed to provide self-protection, from BXT blockade. However, in these instances, as opposed to the [Leu, Pro]NPY-NPY(13-36) cross-protection experiments, the occurrence of protection was probably masked by the relatively large magnitude of desensitization concurrently induced by the protecting peptide. Taken together, the present findings suggest that NPY-induced rat femoral artery vasoconstriction is mediated by separate, BXT-sensitive, postsynaptic Y1 ([Leu, Pro]NPY-activated) and Y2 [NPY(13-36)-activated] receptors.

Animals↗
PubMed1987

[Experimental study of the protective activity of vaccines made from 7 Pseudomonas aeruginosa immunotypes].

Monovaccines were prepared from seven P. aeruginosa immunotypes (according to Fisher's classification) and three P. aeruginosa production strains belonging to immunotypes 2, 3, and 7. The immunogenic potency of these monovaccines was studied in direct and cross experiments on the active protection of mice. The study revealed that the monovaccines prepared from P. aeruginosa of seven immunotypes possessed both specific and cross protective activity. Protective cross activity was revealed also in the vaccines prepared from the production strains. When tested in mice challenged with the corresponding homologous strains, the monovaccines prepared from immunotypes 2, 3, 4 and 7 proved to possess higher immunogenic potency than monovaccines prepared from immunotypes 1, 5 and 6.

Animals↗
PubMed1995

Leishmania pifanoi amastigote antigens protect mice against cutaneous leishmaniasis.

In the search for a leishmaniasis vaccine, extensive studies have been carried out with promastigote (insect stage) molecules. Information in this regard on amastigote (mammalian host stage) molecules is limited. To investigate host immune responses to Leishmania amastigote antigens, we purified three stage-specific antigens (A2, P4, and P8) from in vitro-cultivated amastigotes of Leishmania pifanoi by using immunoaffinity chromatography. We found that with Corynebacterium parvum as an adjuvant, three intraperitoneal injections of 5 micrograms of P4 or P8 antigen provided partial to complete protection of BALB/c mice challenged with 10(5) to 10(7) L. pifanoi promastigotes. These immunized mice developed significantly smaller or no lesions and exhibited a 39- to 1.6 x 10(5)-fold reduction of lesion parasite burden after 15 to 20 weeks of infection. In addition, P8 immunization resulted in complete protection against L. amazonensis infection of CBA/J mice and partial protection of BALB/c mice, suggesting that this antigen provided cross-species protection of mice with different H-2 haplotypes. At different stages during infection, vaccinated mice exhibited profound proliferative responses to parasite antigens and increased levels of gamma interferon production, suggesting that a Th1 cell-mediated immune response is associated with the resistance in these mice. Taken together, the data in this report indicate the vaccine potential of amastigote-derived antigens.

Animals↗
PubMed2004

Cytosolic ascorbate peroxidase 1 is a central component of the reactive oxygen gene network of Arabidopsis.

Reactive oxygen species (ROS), such as O2- and H2O2, play a key role in plant metabolism, cellular signaling, and defense. In leaf cells, the chloroplast is considered to be a focal point of ROS metabolism. It is a major producer of O2- and H2O2 during photosynthesis, and it contains a large array of ROS-scavenging mechanisms that have been extensively studied. By contrast, the function of the cytosolic ROS-scavenging mechanisms of leaf cells is largely unknown. In this study, we demonstrate that in the absence of the cytosolic H2O2-scavenging enzyme ascorbate peroxidase 1 (APX1), the entire chloroplastic H2O2-scavenging system of Arabidopsis thaliana collapses, H2O2 levels increase, and protein oxidation occurs. We further identify specific proteins oxidized in APX1-deficient plants and characterize the signaling events that ensue in knockout-Apx1 plants in response to a moderate level of light stress. Using a dominant-negative approach, we demonstrate that heat shock transcription factors play a central role in the early sensing of H2O2 stress in plants. Using knockout plants for the NADPH oxidase D protein (knockout-RbohD), we demonstrate that RbohD might be required for ROS signal amplification during light stress. Our study points to a key role for the cytosol in protecting the chloroplast during light stress and provides evidence for cross-compartment protection of thylakoid and stromal/mitochondrial APXs by cytosolic APX1.

Arabidopsis↗
PubMed1995

Cross-reactive antibodies have both protective and pathogenic potential.

We report the characteristics of five IgM anti-phosphorylcholine (PC) Abs derived from nonautoimmune BALB/c mice. These Abs were chosen on the basis of their unique ability to cross-react with dsDNA. Three Abs protect mice from a lethal pneumococcal infection, and all five Abs deposit in glomeruli and cause renal dysfunction. Analysis of V region gene usage shows that none of the Abs is encoded by the V1 gene segment used to encode the dominant T15+ anti-PC response typically expressed in serum of PC-immunized BALB/c mice. The demonstration of the existence of noncanonical protective anti-PC Abs that also display pathogenic autoreactivity suggests that idiotypically restricted responses may serve to prevent the expression of Abs that react with both foreign and self Ags and so help maintain self-tolerance.

Amino Acid Sequence↗
PubMed1990

New vaccines against bacterial enteric infections.

During the last 10 years, rapid progress in basic research and biotechnology related to enteric infection has now begun to have a substantial impact on vaccine development against these infections. Two new typhoid vaccines, one for oral administration and the other for injection, which have much fewer and milder side effects than previous whole-cell parenteral vaccines, have become available. An oral cholera vaccine has been developed which, without any adverse reactions at all, confers long-lasting protection against cholera. The new cholera vaccine also, through antitoxic immunologic cross-reactivity, protects significantly against diarrhea caused by enterotoxigenic Escherichia coli (ETEC). Notable progress has also been made towards the development of an oral killed vaccine against ETEC diarrhoea as well as live attenuated vaccines against rotaviruses, cholera and shigellosis.

Bacterial Vaccines↗
PubMed2005

Universal influenza B vaccine based on the maturational cleavage site of the hemagglutinin precursor.

Conventional influenza vaccines can prevent infection, but their efficacy depends on the degree of antigenic "match" between the strains used for vaccine preparation and those circulating in the population. A universal influenza vaccine based on invariant regions of the virus, able to provide broadly cross-reactive protection, without requiring continuous manufacturing update, would solve a major medical need. Since the temporal and geographical dominance of the influenza virus type and/or subtype (A/H3, A/H1, or B) cannot yet be predicted, a universal vaccine, like the vaccines currently in use, should include both type A and type B influenza virus components. However, while encouraging preclinical data are available for influenza A virus, no candidate universal vaccine is available for influenza B virus. We show here that a peptide conjugate vaccine, based on the highly conserved maturational cleavage site of the HA(0) precursor of the influenza B virus hemagglutinin, can elicit a protective immune response against lethal challenge with viruses belonging to either one of the representative, non-antigenically cross-reactive influenza B virus lineages. We demonstrate that protection by the HA(0) vaccine is mediated by antibodies, probably through effector mechanisms, and that a major part of the protective response targets the most conserved region of HA(0), the P1 residue of the scissile bond and the fusion peptide domain. In addition, we present preliminary evidence that the approach can be extended to influenza A virus, although the equivalent HA(0) conjugate is not as efficacious as for influenza B virus.

Amino Acid Sequence↗
PubMed1984

Myocardial protection during prolonged aortic cross-clamping. Comparison of blood and crystalloid cardioplegia.

We compared the ability of blood and crystalloid cardioplegia to protect the myocardium during prolonged arrest. Twelve dogs underwent 180 minutes of continuous arrest. Group I (six dogs) received 750 ml of blood cardioplegic solution (potassium chloride 30 mEq/L) initially and every 30 minutes. Group II (six dogs) received an identical amount of crystalloid cardioplegic solution (potassium chloride 30 mEq, methylprednisolone 1 gm, and 50% dextrose in water 16 ml/L of electrolyte solution). Temperature was 10 degrees C and pH 8.0 in both groups. Studies of myocardial biochemistry, physiology, and ultrastructure were completed before arrest and 30 minutes after normothermic reperfusion. Biopsy specimens for determination of adenosine triphosphate were obtained before, during, and after the arrest interval. Regional myocardial blood flow, total coronary blood flow, and myocardial oxygen consumption were statistically unchanged in Group I (p greater than 0.05). Total coronary blood flow rose 196% +/- 49% in Group II (p less than 0.005), and left ventricular endocardial/epicardial flow ratio fell significantly in this group from 1.51 +/- 0.18 to 0.8 +/- 0.09, p less than 0.01 (mean +/- standard error of the mean. The rise in myocardial oxygen consumption was not significant in this group (34% +/- 36%, p greater than 0.05). Ventricular function and compliance were statistically unchanged in both groups. In Group II, adenosine triphosphate fell 18% +/- 3.4% (p less than 0.005) after 30 minutes of reperfusion; it was unchanged in Group I. Ultrastructural appearance in both groups correlated with these changes. We conclude that blood cardioplegia offers several distinct advantages over crystalloid cardioplegia during prolonged arrest.

Adenosine Triphosphate↗