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At least 1,369 records · Page 76Linked to original sources
PubMed1991

Protective ribosomal preparation from Shigella sonnei as a parenteral candidate vaccine.

A parenteral Shigella ribosomal vaccine (SRV) was investigated in animals for safety, antibody-inducing capacity, and protective activity. Ribosomal preparations from a Shigella sonnei phase I avirulent strain were obtained and shown to possess chemical, sedimentation, and other properties typical of bacterial ribosomes. No endotoxin contamination was revealed by a ketodeoxyoctonate assay, although the presence of some kind of O antigen was evidenced by serological findings and the high activity of SRV in inducing the O-antibody response and immunological memory in animals. SRV was nontoxic in mice, guinea pigs, and monkeys and induced no local reactions when injected subcutaneously in reasonable doses. Significant protection against a local Shigella infection (Sereny test) was seen in guinea pigs injected with SRV (efficiency index, about 60%) and the specificity of the protection was evident from cross-challenge experiments. The protective efficiency of SRV was especially high in rhesus monkeys challenged orally with virulent Shigella cells (89%, as calculated from the summarized data of several experiments in 71 animals). Protection in monkeys was long lasting and could be demonstrated several months after injection of SRV. An inexpensive technique can be used for the production of SRV on a large scale. The high immunogenicity of SRV is discussed in terms of the amplifying effect of the ribosome, which serves as a delivery system for polysaccharide O antigen. Further study of SRV as a candidate vaccine for humans seems justified by the data obtained.

Animals↗
PubMed1989

Cross-reacting antigens to Pc96, a protective antigen of Plasmodium chabaudi, in P. falciparum, P. vivax, and P. cynomolgi.

Mice can be partially protected against Plasmodium chabaudi by immunization with the antigen Pc96, isolated from the erythrocyte membranes of infected mice. We used a Pc96 specific monoclonal antibody to identify antigens which cross-react with Pc96 in P. falciparum, P. vivax, and P. cynomologi. The cross-reactive molecules are antigens of Mr 155,000 in P. falciparum, Mr 220,000 in P. cynomologi. They are located in the surface membranes of infected erythrocytes. Pc96 is characterized by immunoelectron microscopy and epitope mapping.

Animals↗
PubMed2005

Protective environments and health status: cross-talk between human and animal studies.

Although aging populations tend to have increased prevalence of a diversity of diseases and disabilities, there are substantial numbers of people who, nevertheless, maintain good health into old age. Human studies frequently demonstrate associations between environmental factors, particularly supportive social environments, and positive states of health. Identifying the pathways from protective social environments to reduced disease risk necessitates the use of animal models as a basis of explanation and a source of suggestions for further human research. We present two examples of this kind of cross-talk: (i) the possibility that the success of well-being therapy following pharmacological treatment for depression as a means of preventing recurrent depressive episodes is based on the stimulation of enrichment of dendritic networks in the hippocampus and spine retraction in the basolateral amygdala; (ii) the possibility that the release of intracerebral oxytocin is a mediating factor between persistently supportive social environments and reduced disease in later life, as exemplified by low levels of allostatic load.

Animals↗
PubMed2002

Comparable bioavailability of two esophago-gastric protective formulations containing pamidronate. A cross-over trial in healthy young adults.

The net absorbable amount of pamidronate (APD), according to AUC values assessed in blood, in the customary dose interval of 24 hours, was found to be similar in 8 healthy young volunteers, who received single doses of 3 capsules of 100 mg APD (AUC0-24 = 510.3 +/- 91.5 micrograms/L x h-1) and 2 tablets of 150 mg (AUC0-24 = 580.5 +/- 117.6 micrograms/L x h-1; p = 0.58) in the fasting state. Both formulations present acid-resistant coatings, designed to protect the mucosa of the upper digestive system from contact with insoluble particles of the bisphosphonates. Tmax values were different, and Cmax values presented a wide inter-individual variation, so that both formulations were not strictly bioequivalent. However, these latter factors were of minor clinical importance given the kinetic features of the bisphosphonates. In conclusion, both formulations afforded comparable bioavailability; that is to say that they can provide a sufficient amount of APD within the studied dose interval, so as to cause similar clinical effects.

Administration, Oral↗
PubMed2000

Arthritis protective regulatory potential of self-heat shock protein cross-reactive T cells.

Immunization with heat shock proteins has protective effects in models of induced arthritis. Analysis has shown a reduced synovial inflammation in such protected animals. Adoptive transfer and immunization with selected T cell epitopes (synthetic peptides) have indicated the protection to be mediated by T cells directed to conserved hsp epitopes. This was shown first for mycobacterial hsp60 and later for mycobacterial hsp70. Fine specificity analysis showed that such T cells were cross-reactive with the homologous self hsp. Therefore protection by microbial hsp reactive T cells can be by cross-recognition of self hsp overexpressed in the inflamed tissue. Preimmunization with hsp leads to a relative expansion of such self hsp cross-responsive T cells. The regulatory nature of such T cells may originate from mucosal tolerance maintained by commensal flora derived hsp or from partial activation through recognition of self hsp as a partial agonist (Altered Peptide Ligand) or in the absence of proper costimulation. Recently, we reported the selective upregulation of B7.2 on microbial hsp600 specific T cells in response to self hsp60. Through a preferred interaction with CTLA-4 on proinflammatory T cells this may constitute an effector mechanism of regulation. Also, regulatory T cells produced IL10.

Adoptive Transfer↗
PubMed1981

Myocardial protection from permanent injury during aortic cross-clamping: effectiveness of pharmacological cardiac arrest combined with topical cardiac hypothermia.

In two groups of animals (6 and 9 dogs), the aorta was cross-clamped 60 and 90 minutes, respectively, during hypothermic cardiopulmonary bypass. Immediately after cross-clamping, pharmacological cardiac arrest was induced by injecting 100 ml of a cold cardioplegic solution into the aortic root. Topical cardiac hypothermia was added. In hearts undergoing 90 minutes of ischemia, a repeat injection of the cardioplegic solution was done at 45 minutes. In 14 dogs (control group), only topical cardiac hypothermia was instituted for myocardial protection during 60 minutes of ischemia. Seven weeks after operation the surviving animals (6 in each group) were killed. Study of myocardial performance failed to demonstrate significant differences among the groups. Microscopic examination of transmural samples taken from anatomically defined sides of both ventricles, disclosed isolated, punctuate subendocardial scars in only 2 hearts of the control group. All the hearts having 90 minutes of pharmacological cardiac arrest and topical cardiac hypothermia exhibited diffuse fibrosis replacing 10 to 20% of the left ventricular myocardium. Extent and incidence of fibrosis were significantly higher in these hearts in comparison to those of the other groups. We conclude that pharmacological cardiac arrest plus topical cardiac hypothermia makes a safe and efficient method of myocardial protection during aortic cross-clamping only if the ischemic intervals is limited to 60 minutes. It cannot prevent permanent myocardial injury if the ischemic arrest is extended to 90 minutes.

Animals↗
PubMed1989

[Mechanism of action of interferon is linked to its ability to protect the cell from interstrand cross-linking of DNA, induced by 8-methoxypsoralen, activated by long-wave UV-light].

Treatment of human lymphocytes in the G1 phase of mitotic cycle with human lymphoblastoid interferon (Ly-IFN) decreased the frequencies of chromosome aberrations induced by 8-methoxy-psoralen-induced interstrand cross-links. Anticlastogenic effect of Ly-IFN was accompanied by stimulation of unscheduled synthesis of DNA in the G2 phase of mitotic cycle, as shown by increased percent of labeled cells registered by 3H-thymidine autoradiography. The data obtained seem to indicate that the mechanism of Ly-IFN protection is connected with stimulation of postreplicative repair.

Chromosome Aberrations↗
PubMed2001

Cross-reactive, cell-mediated immunity and protection of chickens from lethal H5N1 influenza virus infection in Hong Kong poultry markets.

In 1997, avian H5N1 influenza virus transmitted from chickens to humans resulted in 18 confirmed infections. Despite harboring lethal H5N1 influenza viruses, most chickens in the Hong Kong poultry markets showed no disease signs. At this time, H9N2 influenza viruses were cocirculating in the markets. We investigated the role of H9N2 influenza viruses in protecting chickens from lethal H5N1 influenza virus infections. Sera from chickens infected with an H9N2 influenza virus did not cross-react with an H5N1 influenza virus in neutralization or hemagglutination inhibition assays. Most chickens primed with an H9N2 influenza virus 3 to 70 days earlier survived the lethal challenge of an H5N1 influenza virus, but infected birds shed H5N1 influenza virus in their feces. Adoptive transfer of T lymphocytes or CD8(+) T cells from inbred chickens (B(2)/B(2)) infected with an H9N2 influenza virus to naive inbred chickens (B(2)/B(2)) protected them from lethal H5N1 influenza virus. In vitro cytotoxicity assays showed that T lymphocytes or CD8(+) T cells from chickens infected with an H9N2 influenza virus recognized target cells infected with either an H5N1 or H9N2 influenza virus in a dose-dependent manner. Our findings indicate that cross-reactive cellular immunity induced by H9N2 influenza viruses protected chickens from lethal infection with H5N1 influenza viruses in the Hong Kong markets in 1997 but permitted virus shedding in the feces. Our findings are the first to suggest that cross-reactive cellular immunity can change the outcome of avian influenza virus infection in birds in live markets and create a situation for the perpetuation of H5N1 influenza viruses.

Adoptive Transfer↗
PubMed1976

Inhibition of peptidoglycan cross-linking in growing cells of Escherichia coli by penicillins and cephalosporins, and its prevention by R factor-mediated beta-lactamase.

The degree of peptidoglycan cross-linking has been studied in growing cells of a Dap(-) Lys(-) auxotroph of Escherichia coli K-12 by following the incorporation of [(3)H]diaminopimelic acid into the lysozyme digestion products of crude, isolated peptidoglycan. The percentage of inhibition of cross-linking increases with increasing concentrations of penicillin G, cephaloridine, and cefuroxime. When the R factor R1drd 19 was introduced into the strain by conjugation, it was found that the type IIIa, beta-lactamase specified by the plasmid was able to protect the cross-linking target against inhibition by penicillin G but not against cephaloridine, even though the beta-lactamase hydrolyzes this substrate 50% faster than penicillin G. Cefuroxime, which is completely resistant to hydrolysis by the type IIIa beta-lactamase, inhibited the peptidoglycan cross-linking target in both the R(+) and R(-) variants of the assay strain. A mutant plasmid, R1drd19amp2, which specified no type IIIa beta-lactamase synthesis, could not provide protection of the cross-linking target against penicillin G. The significance of these results, in relation to the ability of the antibiotics to pass the permeability barrier of the bacterial envelope, is discussed.

Amidohydrolases↗
PubMed1994

Regional deep hypothermia of the spinal cord protects against ischemic injury during thoracic aortic cross-clamping.

We tested in pigs the hypothesis that regional deep hypothermia of the spinal cord achieved by cerebrospinal fluid cooling will protect against ischemic injury during thoracic aortic cross-clamping. Eight control animals underwent aortic cross-clamping at the distal aortic arch and just above the diaphragm for 30 minutes. Eight experimental animals had placement of two subarachnoid perfusion catheters through laminectomies at T4 and the lower lumbar region. The subarachnoid space was perfused with normal saline solution at 6 degrees C delivered by gravity infusion, with infusion rates adjusted to maintain cord temperatures at less than 20 degrees C. After 30 minutes of aortic cross-clamping, the infusion was stopped and the cord allowed to warm to body temperature. Hind limb neurologic function was graded by Tarlov's scale. All of the animals in the control group had complete hind limb paraplegia (Tarlov grade 0) postoperatively. Seven of the 8 animals in the experimental group had preservation of hind limb motor function (Tarlov grade 2), and 1 animal had complete hind limb paraplegia (Tarlov grade 0) (p = 0.002, Fisher's exact test). We conclude that regional deep hypothermia of the spinal cord in pigs does provide some protection from ischemic injury during thoracic aortic cross-clamping. Clinically this may be a useful adjunct for prevention of paraplegia during thoracic aortic operations.

Animals↗
PubMed2001

Unilateral hearing losses alter loud sound-induced temporary threshold shifts and efferent effects in the normal-hearing ear.

In animals with bilaterally normal hearing, olivocochlear pathways can protect the cochlea from the temporary shifts in hearing sensitivity (temporary threshold shifts; TTSs) caused by short-duration intense loud sounds. The crossed olivocochlear pathway provides protection during binaural loud sound, and uncrossed pathways protect when monaural or binaural loud sounds occur in noise backgrounds. Here I demonstrate that when there is a chronic unilateral hearing loss, effects of loud sounds, and efferent effects on loud sound, in the normal-hearing ear differ markedly from normal. Three categories of test animals with unilateral hearing loss were tested for effects at the normal-hearing ear. In all categories a monaural loud tone to the normal-hearing ear produced lower-than-normal TTSs, apparently because of a tonic re-setting of that ear's susceptibility to loud sound. Second, in the two test categories in which the hearing-loss ear was only partly damaged, binaural loud sound exacerbated TTSs in the normal-hearing ear because it caused threshold shifts that were a combination of "pure" TTSs and uncrossed efferent suppression of cochlear sensitivity. (In normal cats, this binaural tone results in crossed olivocochlear protection that reduces TTS.) Binaural loud sound did not produce such uncrossed efferent effects in the test category in which the nontest ear had suffered total hearing loss, suggesting that this uncrossed efferent effect required binaural input to the CNS. It is noteworthy that, in the absence of this uncrossed efferent suppression, the pure loud sound-alone induced TTSs after binaural exposure were low. Thus in the absence of any efferent effect, the normal-hearing cochlea had a reduced susceptibility to loud tone-induced damage. Finally, the results suggest that, with respect to cochlear actions at high sound levels, uncrossed and crossed efferent pathways may exert different effects at the one type of receptor cell.

Animals↗
PubMed2000

Strategies for inducing protection against avian influenza A virus subtypes with DNA vaccines.

The cross-species transfer of a H5N1 influenza virus from birds to humans, and the systemic spread of this virus in mice, has accelerated the efforts to devise protective strategies against lethal influenza viruses. DNA vaccination with the highly conserved nucleoprotein gene appears to provide cross protection against influenza A viruses in murine models. Whether such vaccines would protect human hosts against different influenza A viruses, including strains with pandemic potential, is unclear. Our aim in this study is to evaluate the ability of a combination DNA vaccine consisting of two plasmids encoding the HA genes from two different subtypes and a DNA vaccine encoding the viral nucleoprotein gene from a H5 virus to induce protection against highly lethal infection caused by H5 and H7 influenza viruses in chickens. Chickens given a single dose of plasmids expressing H5 and H7 hemagglutinins protected the birds from infection by either subtype. However, birds immunized with nucleoprotein DNA and challenged with either A/Ck/Vic/1/85(H7N7) or A/Ty/Ir/1/83 (H5N8) showed definite signs of infection, suggesting inadequate immunity against viral infection. Fifty percent of the nucleoprotein DNA immunized birds survived infection by influenza A/Ty/Ir/1/83 (H5N8) virus (virus of same subtype) while 42% survived infection by influenza A/Ck/Vic/1/85/(H7N7) virus (virus of a different subtype). These studies demonstrate that immunization with DNA encoding a type-specific gene may not be effective against either homologous or heterologous strains of virus, particularly if the challenge virus causes a highly lethal infection. However, the combination of HA subtype vaccines are effective against lethal infection caused by viruses expressing any of the HA subtypes used in the combination preparation.

Animals↗
PubMed1999

Brominated 7-hydroxycoumarin-4-ylmethyls: photolabile protecting groups with biologically useful cross-sections for two photon photolysis.

Photochemical release (uncaging) of bioactive messengers with three-dimensional spatial resolution in light-scattering media would be greatly facilitated if the photolysis could be powered by pairs of IR photons rather than the customary single UV photons. The quadratic dependence on light intensity would confine the photolysis to the focus point of the laser, and the longer wavelengths would be much less affected by scattering. However, previous caged messengers have had very small cross sections for two-photon excitation in the IR region. We now show that brominated 7-hydroxycoumarin-4-ylmethyl esters and carbamates efficiently release carboxylates and amines on photolysis, with one- and two-photon cross sections up to one or two orders of magnitude better than previously available. These advantages are demonstrated on neurons in brain slices from rat cortex and hippocampus excited by glutamate uncaged from N-(6-bromo-7-hydroxycoumarin-4-ylmethoxycarbonyl)-L-glutamate (Bhc-glu). Conventional UV photolysis of Bhc-glu requires less than one-fifth the intensities needed by one of the best previous caged glutamates, gamma-(alpha-carboxy-2-nitrobenzyl)-L-glutamate (CNB-glu). Two-photon photolysis with raster-scanned femtosecond IR pulses gives the first three-dimensionally resolved maps of the glutamate sensitivity of neurons in intact slices. Bhc-glu and analogs should allow more efficient and three-dimensionally localized uncaging and photocleavage, not only in cell biology and neurobiology but also in many technological applications.

Animals↗
PubMed1997

Protective cellular immunity: cytotoxic T-lymphocyte responses against dominant and recessive epitopes of influenza virus nucleoprotein induced by DNA immunization.

DNA immunization offers a novel means to induce cellular immunity in a population with a heterogeneous genetic background. An immunorecessive cytotoxic T-lymphocyte (CTL) epitope in influenza virus nucleoprotein (NP), residues 218 to 226, was identified when mice were immunized with a plasmid DNA encoding a full-length mutant NP in which the anchor residues for the immunodominant NP147-155 epitope were altered. Mice immunized with wild-type or mutant NP DNA were protected from lethal cross-strain virus challenge, and the protection could be adoptively transferred by immune splenocytes, indicating the role of cell-mediated immunity in the protection. DNA immunization is capable of eliciting protective cellular immunity against both immunodominant and immunorecessive CTL epitopes in the hierarchy seen with virus infection.

Animals↗