Biological characterization of an immunosuppressant from group A streptococci.

A component in extracts of Group A streptococci suppresses antibody formation in mice against heterologous erythrocyte and protein antigens. Large doses are not toxic and repeated injection does not change its effectiveness. It is most effective when injected 1 or 2 days before antigen and it is not suppressive when given after antigen. The active factor occurs as a large polydisperse complex and activity can be increased 10- to 25-fold by filtration through Sepharose 2B. Both direct (gammaM) and indirect (gammaG) antibody-forming cells are suppressed in primary and secondary responses. Injection before a primary response does not reduce memory cell development. It increases rather than depresses the "background" antibody-forming cells to sheep erythrocytes, and is equally effective if injected intraperitoneally or intravenously. Ribonuclease increases activity while deoxyribonuclease has no effect. Proteases destroy immunosuppressive action.

Immunosuppressant from group A streptococci.

A cytoplasmic component of group A streptococci suppresses both 19S and 7S antibody responses of mice to sheep erythrocytes. Partial purification is achieved by differential centrifugation and gel filtration. When the direct and indirect hemolytic plaque techniques are used, a single injection of this group A material given before injection of erythrocytes produces more than 90-percent suppression of either primary or secondary immune response.

Clinical course in infants diagnosed with transient tachypnea of newborn: A clinical trial assessing the role of conservative versus conventional management.

BACKGROUND: Transient tachypnea of the newborn (TTN) is a respiratory disorder secondary to inadequate or delayed clearance of lung fluids. Early symptoms of the disease are indistinguishable from neonatal respiratory distress syndrome, pneumonia, and persistent pulmonary hypertension. Therefore, these newborns, in addition to receiving conservative management, receive antibiotics until blood cultures provide definite results. In this study, we assessed the clinical course of neonates diagnosed with TTN who received conventional versus conservative management. METHODS: One hundred and thirty neonates diagnosed as having TTN were randomly enrolled in two study groups. While patients belonging to one group received conservative management, those from the other group were treated with conventional medical therapy. RESULTS: Mean duration of hospitalization was 7 ± 0.2 in the conventional and 5 ± 1.5 in the conservative group. Duration of antibiotic therapy was 6.7 ± 2.47 days in the conventional group. CONCLUSION: Newborns diagnosed with TTN without prenatal risk factors and a negative C reactive protein test do not need to be administered antibiotics and hospitalized until confirmatory blood culture results are obtained.

Immunologic reconstitution in severe combined immunodeficiency following transplantation with parental bone marrow.

A 9-month-old girl with severe combined immunodeficiency was transplanted with BM cells from her father. The child had complete restoration of cell-mediated immune functions. Humoral immune functions remain absent nine months after transplant. Child and father were HL-A identical and their lymphocytes were nonreactive in mixed lymphocyte culture. The parents of the child were first cousins and shared an HL-A haplotype. In countries like Lebanon, where there is a high incidence of first-cousin marriages (15%) and where villages are relatively isolated, the search for histocompatible graft donors should extend beyond the siblings to other members of the family.

An erythrocyte-sensitising antigen from Vibrio cholerae.

Erythrocyte-sensitising antigens (AE) were prepared from Vibrio cholerae serotypes, from EL-Tor vibrio, Escherichia coli and Salmonella enteritidis by digesting the organisms with NaOH followed by precipitation with alcohol. When AE was used in indirect haemagglutination (IHA) tests, the results in a number of cases were somewhat more sensitive and more specific than those obtained in classical agglutination tests. No cross reactions occurred between V. cholerae serotypes and E. coli and S. enteritidis. Much of the reactive part of the AE was not sedimentable at 100,000 g for 1 h. The eluant from the B. cholerae AE on Sephadex G-200 yielded three fractions, one of which was the most active in IHA tests. Treatment of the AE with trypsin resulted in an appreciable increase in the heterotypic serum titres in IHA tests. The spectrophotometric absorption of the AE at 260 nm showed a hump that may have been indicative of the presence of nucleic acid. Treatment of the antigen with ribonuclease reduced its nucleic acid content but did not change to any significant extent the reactivity of the preparation. The AE antigen of V. cholerae was Molisch-positive and was capable of sensitising untanned erythrocytes in IHA tests. It is suggested that the reactive part of the AE antigen is a carbohydrate complex.

Discovery of novel inhibitors of the ZipA/FtsZ complex by NMR fragment screening coupled with structure-based design.

ZipA is a membrane anchored protein in Escherichia coli that interacts with FtsZ, a homolog of eukaryotic tubulins, forming a septal ring structure that mediates bacterial cell division. Thus, the ZipA/FtsZ protein-protein interaction is a potential target for an antibacterial agent. We report here an NMR-based fragment screening approach which identified several hits that bind to the C-terminal region of ZipA. The screen was performed by 1H-15N HSQC experiments on a library of 825 fragments that are small, lead-like, and highly soluble. Seven hits were identified, and the binding mode of the best one was revealed in the X-ray crystal structure. Similar to the ZipA/FtsZ contacts, the driving force in the binding of the small molecule ligands to ZipA is achieved through hydrophobic interactions. Analogs of this hit were also evaluated by NMR and X-ray crystal structures of these analogs with ZipA were obtained, providing structural information to help guide the medicinal chemistry efforts.

A potent antimitogenic factor from group A streptococci.

A cytoplasmic component from group A streptococci produced complete suppression of human lymphocyte transformation induced by phytohaemagglutinin or the mixed lymphocyte reaction in vitro. It also suppressed antibody-forming cells in mice against sheep erythrocytes. The active substance was eluted as second and third fractions form Sephadex G-200 chromatography of the 100,000 g supernatant of sonically ruptured group A streptococci. The antimitogenic activity was not susceptible to trypsin, pronase, RNase or DNase digestion, but the activity was completely lost when it was sequentially digested, first with RNase and DNase and then with pronase. The active substance was not antigenic nor heat-labile at 56 degrees. It may be a protein component of a nucleoprotein.

The host response in secondary hydatidosis of mice. II. Cell mediated immunity.

The presence of cell mediated immunity to Echinococcus granulosus antigen was detected in syngeneic mice with secondary hydatidosis. Significant increases of thymidine uptake were observed in spleen cells from infected animals exposed to protoscolex or hydatid fluid antigens. A definite decrease in the number and size of cysts occurred in mice following the simultaneous intraperitoneal injection of viable protoscolices and a suspension of 1 x 10(7) sensitized spleen cells.

Genetics of cell-mediated lympholysis in man.

Cell-mediated lympholysis (CML) was studied in a family containing two siblings in who genetic recombinaiton had occurred in the HLA comples. In one sibling, recombination occurred between the HLA-A locus and the HLA-B locus. In the second sibling recombination occurred between the HLA-B locus and the HLA-D locus. Strong CML activity was generated in mixed lymphocyte cultures (MLC) when stimulator and responder cells differed in HLA-A, B, and D antigens. MLC involving HLA-D differences alone did not generate CML. Weak, but definite CML activity was generated during MLC with cells differing at HLA-A and HLA-B but sharing HLA-D. HLA-B antigens were good targets for lysis in all combinations studied. HLA-A antigens were poor targets in some but not in all combinations. However, combinations where HLA-A antigens seemed to be good targets could have involved HLA-B differences due to polymorphism of HLA-B7 antigens each inherited from a different parent. HLA-D antigens did not serve as targets for lysis. In three cell experiments, excellent CML activity was generated when responder cells were stimulated by HLA-D antigens and by HLA-A and B antigens present on separate stimulator cells.