Polyclonal antibodies from blood and cerebrospinal fluid of patients with multiple sclerosis effectively hydrolyze DNA and RNA

It is known that in the blood of patients with some autoimmune diseases catalytically active antibodies hydrolyzing proteins, DNA, and RNA may be detected. In the present work homogeneous preparations of IgG antibodies (Ab) possessing high affinity for nucleic acids (NA) were obtained for the first time from blood and cerebrospinal fluid of patients with multiple sclerosis (MS). The fraction of IgG Ab as well as its Fab fragments and isolated light chains of both kappa- and lambda-types were shown to catalyze effectively the hydrolysis of DNA and RNA. It is shown by different methods that the capability for nucleic acid hydrolysis is an intrinsic property of the polyclonal Ab. NA-hydrolyzing Ab were detected in the blood of 69 of 72 and in the cerebrospinal fluid of 5 of 5 examined MS patients, while they were not detected in the blood of any of 50 healthy donors examined. Comparison of relative rates of RNA hydrolysis and of the substrate specificity in hydrolysis of various model RNAs--cCMP, poly(U), poly(A), and poly(C)--revealed pronounced differences of MS antibodies from ribonucleases of human blood, ribonuclease A, and all earlier described abzymes. The abzymes are usually characterized by relatively low specific activities in comparison with that of normal enzymes catalyzing analogous reactions. Ab from the blood of MS patients are the first example of autoabzymes whose specific activity in RNA hydrolysis is comparable or even higher than that of pancreatic ribonuclease A--one of the most active RNA-hydrolyzing enzymes.     

Evaluation of the role of the Yersinia pestis plasminogen activator and other plasmid-encoded factors in temperature-dependent blockage of the flea

Yersinia pestis, the plague bacillus, has a plasminogen activator (pla) gene on the 9.5-kb plasmid pPla that is hypothesized to play a role in producing the foregut blockage in the flea vector that precedes transmission. In this study, however, Y. pestis that lacked pPla, the 70-kb virulence plasmid, or both plasmids, proved able to block Xenopsylla cheopis fleas normally. Blockage rates decreased with increasing environmental temperature for fleas infected with either wild type or pPla- Y. pestis. Thus, procoagulant ability of the Y. pestis pla gene product does not mediate blockage, nor does its ability to induce fibrinolysis at>28 degreesC account for failure to block at elevated temperatures. A Y. pestis strain that lacked all or part of the third plasmid of 110 kb, however, failed to colonize the flea midgut normally, indicating that one or more genes on the large plasmid may be required for vectorborne transmission.     

Pharmacological properties of homomeric and heteromeric GluR1o and GluR3o receptors

Homomeric and heteromeric alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor subunits GluR1o and GluR3o were expressed in Spodoptera frugiperda (Sf9) insect cells. Membranes containing the recombinant receptors showed a doublet of bands of the expected size (99-109 kDa) after western immunoblotting which was shifted to a single band upon deglycosylation. In (R,S)-[3H]AMPA binding experiments, high expression was seen (Bmax = 0.8-3.8 pmol/mg protein) along with high affinity binding to a single site (Kd, nM+/-S.D.): GluR1o, 32.5+/-2.7; GluR3o, 23.7+/-2.4; GluR1o + GluR3o, 18.1+/-2.9. The pharmacological profiles of these receptors resembled that of native rat brain AMPA receptors: AMPA analogues > L-glutamate > quinoxaline-2,3-diones > kainate. In the Xenopus oocyte expression system we had previously shown that the agonist (R,S)-2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionate (ACPA) exhibited an 11-fold selectivity for GluR3o vs. GluR1o. In this study, it was found that ACPA has 3-fold higher affinity at homomeric GluR3o and heteromeric receptors than at homomeric GluR1o, suggesting that its efficacy and/or desensitisation properties are different at GluR1o vs. GluR3o.     

Derepressed alloantigen in transplacentally induced lung tumor coded for by H-2 linked gene

A transplacentally induced lung tumor of strain C3Hf mice grows progressively when transplanted to (C3Hf X A)F1 hybrid mice but not when transplanted to C3Hf recipients. Progressive tumor growth occurs in [(C3Hf X A)F1 X C3Hf] backcross mice inheriting the H-2a haplotype from the F1 parent. Furthermore, radioresistant immunity to the lung tumor can be induced in C3Hf mice by immunization with normal tissue of B10.A and B10.A(2R) but not of B10 or B10.A(5R) strain mice.     

Endotoxic activity of cell-free rumen fluid from cattle fed hay or grain

The cell-free rumen fluid from cattle fed hay or grain exhibited the following biological characteristics which strongly suggest the presence of endotoxin or a toxic principle similar to endotoxin of gram-negative bacteria: proved lethal to mice when injected with actinomycin D; proved extremely lethal to chick embryo; induced biphasic pyogenic response in rabbits; enhanced susceptibility to bacterial infection in mice; evoked positive epinephrine skin reaction in rabbits and phenol-water or aqueous ether proved lethal to mice and chick embryos. A quantitative difference in concentrations of endotoxin was observed on LD50 in mice and chick embryos and response to the epinephrine skin test in rabbits. Cell-free rumen fluid of grain-fed cattle contained at least twice as much endotoxin as that of hay-fed cattle. Endotoxin in cell-free rumen fluid and in higher concentration in cattle fed grain than in those fed hay support the hypothesis that rumen bacterial endotoxins may participate in the pathogenesis of diseases associated with high grain feeding such as lactic acidosis and the sudden-death syndrome.     

A longitudinal examination of computer self-efficacy change trajectories during training

Computer self-efficacy (CSE) is known to enhance individual competence and performance in learning and using technology as well as improve technology attitudes and beliefs. Using longitudinal studies, CSE increases over time during organizational technology training. While these studies have been instrumental in our understanding of how self-efficacy operates in organizations, some critical questions remain unanswered. In particular these studies cannot answer how long it takes for one’s CSE to increase during training, nor can it describe the shape of the change trajectory (linear? some other shape?). The answers to these questions will provide organizations a much clearer perspective on training expectations, understanding when benefits from training through enhanced CSE might be expected, and when to start and ramp up/down training efforts. This study examines these issues by collecting repeated waves of data from 230 respondents in a technology lab training setting and using a relatively new structural equation modeling technique, latent growth modeling. Findings suggest that it takes about 2 months of training for individuals to display significant increases in CSE, and that the growth trajectory for CSE in non-linear. In the proposed model, anxiety is a significant predictor of CSE change, while CSE change significantly predicted software-specific self-efficacies.