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Biomedical subjects

K McIntosh

Publications and source records attributed to K McIntosh.

207 records · Page 12Linked to original sources

Morphogenesis of avian infectious bronchitis virus and a related human virus (strain 229E).

Avian infectious bronchitis virus (IBV) and strain 229E, a virus recently recovered from patients with colds, have been shown to possess a similar distinctive morphology in negatively stained preparations. An electron microscopic study of the morphogenesis of IBV in the chorioallantoic membrane and of strain 229E in WI-38 cells was performed. In infected cells, round electron-dense particles 82 mmu in diameter were observed to form by a process of budding from membranes of the endoplasmic reticulum and cytoplasmic vesicles. The particles in IBV-infected cells were similar in size and shape to those in strain 229E-infected cells but showed certain differences in internal structure. The evidence that the particles represent virions and the implications of these findings in the classification of this virus group are discussed.

Animals↗

Total lymphoid irradiation and antigen-specific tolerance: future therapy for experimental myasthenia gravis?

Total lymphoid irradiation (TLI) is effective in the immunosuppressive treatment of human and experimental autoimmune disorders, including experimental autoimmune myasthenia gravis (EAMG). Under certain circumstances. TLI may facilitate the induction of specific tolerance to antigens present during or shortly after the TLI treatment. This study was designed to determine whether TLI could induce or enhance tolerance to acetylcholine receptor (AChR), the antigen in myasthenia gravis, or to other antigens. We presented the antigens in various potentially tolerogenic forms to rats that were first pre-treated with TLI, or controls treated with sham irradiation. Injection of deaggregated human gamma globulin (HGG), a classical tolerogen, was most effective; it produced antigen-specific tolerance, which was significantly enhanced by pre-treatment with TLI. Injection of HGG coupled to rat peritoneal cells induced a moderate degree of specific tolerance; in this case, pre-treatment with TLI added only nonspecific suppression. In contrast, AChR, either in solubilized form with no adjuvant, or coupled to syngeneic rat peritoneal cells, failed to induce tolerance, and actually primed the immune system, when given alone or in conjunction with TLI. Subsequent challenge with AChR resulted in an enhanced (secondary) anti-AChR antibody response. These results show that the nature of the antigen itself may predispose to tolerance or to immune stimulation. AChR appears to be highly immunogenic. However, if a tolerogenic fragment or form of AChR can be identified, its use in combination with TLI may result in specific tolerance. If such specific tolerance can be induced during an ongoing autoimmune reaction to AChR, it would be an effective treatment for myasthenia gravis.

Animals↗

Feasible improvements in vaccines in the Expanded Programme on Immunization.

Feasible improvements in existing vaccines of the Expanded Programme on Immunization are reviewed. The toxicity of pertussis vaccines can probably be reduced and the immunogenicity increased by recently instituted improvements in purity and selectivity. Candidate vaccines containing inactivated pertussis toxin, with or without other components, are in use in Japan and in controlled trials elsewhere. Inactivated poliovirus vaccines have been improved over the past decade and presently show promise of inducing immunity with as few as two doses administered in infancy. At the same time, improved methods for delivering the oral poliovirus vaccine through mass vaccination campaigns are being increasingly employed throughout the developing world. Major improvements in the measles vaccine will probably come from the development of new stabilizers and the use of vaccines that are immunogenic in the presence of maternal antibody.

Diphtheria Toxoid↗

Pathogenesis of severe acute respiratory infections in the developing world: respiratory syncytial virus and parainfluenza viruses.

Respiratory syncytial virus (RSV) and parainfluenza viruses (PIVs) are the most frequently isolated pathogens in infants and children with acute lower respiratory infection (LRI) in the developed world. Less information is available about their importance in LRI in the developing world, but they are probably important there also. The pathogenesis of viral bronchiolitis and pneumonia involves inoculation and early replication in the upper respiratory tract, followed by aspiration into the lower respiratory tract when both the mucosal and systemic immune systems are involved in a specific response. Both disease and recovery reflect processes of viral replication (with attendant cellular destruction) and of immune response (with attendant direct cellular destruction and release of pathogenic, along with beneficial, mediators). Factors predisposing to bacterial superinfection are poorly understood except in animal models. Conditions leading to heightened susceptibility to severe disease in the developed world are particularly common in the developing world. Increasing information on RSV and PIV infections in the developing world will likely point to their importance. Strategies for prevention of severe illnesses due to these viruses will follow from concepts elucidated through animal models and studies of infants in the developed world.

Acute Disease↗

Antigenicity and reactogenicity of influenza A/USSR/77 virus vaccine in children--a multicentered evaluation of dosage and safety.

Clinical trials of monovalent A/USSR/77 (H1N1) and trivalent A/USSR/77 (H1N1), A/Texas/77 (H3N2), and B/Hong Kong/72 inactivated influenza virus vaccines were carried out in 358 children and adolescents. Only split-virus vaccines were administered to children younger than 13 years of age. No serious local or systemic reactions were observed among the study participants. Two doses of vaccine containing 7-20 micrograms of the A/USSR/77 (H1N1) viral antigen were required to achieve serum titers of hemagglutinin-inhibiting (HA1) antibody greater than 1:40. However, single doses containing 7-20 micrograms of the A/Texas/77 (H3N2) or B/Hong Kong/72 antigens stimulated serum HAI antibody levels of 1:40.

Adolescent↗

Selective primary health care: strategies for control of disease in the developing world. XXI. Acute respiratory infections.

Acute respiratory infections represent an important cause of mortality in developing countries, especially among malnourished infants. The microbial etiologies are numerous and complex. Since vaccines effective against the likely major pathogens in the youngest children are not available, the acute respiratory infection control programs designed by the World Health Organization are based on simple schemes to classify illness according to severity and to treat bacterial infections early, thus preventing severe complications. These programs require careful planning to anticipate and circumvent local problems, and their efficacy should be monitored with care. In addition, research is needed in many areas: definition of the spectrum of organisms involved and the pathogenesis of severe infection; delineation of markers that will accurately identify patients needing antibiotics or hospitalization; performance of controlled trials of intervention strategies that will unequivocally identify effective methods; design and production of new, simple, and inexpensive diagnostic tools; and development of vaccines that will be effective in the target populations.

Adolescent↗

Pathogens associated with acute lower respiratory tract infection in young children.

To determine the agents associated with acute lower respiratory infection in young children, we studied 102 hospitalized children less than 5 years old using culture and serology for viruses and Chlamydia trachomatis, fluorescent antibody testing for pertussis and respiratory syncytial virus, blood cultures and counterimmunoelectrophoresis of nasopharyngeal secretions and urine for pneumococcal and Haemophilus influenzae type b antigens. At least one agent was detected in 87 children and multiple agents were found in 33. Viruses were detected 80 times; respiratory syncytial virus was most common (61 cases) and was detected as often by fluorescent antibody testing as by culture. C. trachomatis was detected in 10 children; all were less than 4 months old and 9 had mixed infections. Bacteria were detected 32 times, were usually pneumococcus (23) or H. influenzae (5) and were detected more often by counterimmunoelectrophoresis than by blood culture. Compared with children yielding only C. trachomatis or viruses, those with bacteria were significantly more likely to have fever, a band count over 2000/mm3 and radiographic consolidation. In this study acute lower respiratory infection was associated commonly with viruses, often with multiple pathogens but not with C. trachomatis after 4 months of age.

Child, Preschool↗

Unusual patterns of serum antibodies to Streptococcus equi in two horses with purpura hemorrhagica.

An enzyme-linked immunosorbent assay (ELISA) was developed for use in horses to determine serum titers of antibodies of the immunoglobulin classes IgA, IgG, and IgM to Streptococcus equi M-like protein and culture supernatant protein antigens. Serum antibodies were determined in 28 adult horses, including 9 horses with recent S. equi infections, 17 horses without known exposure to S. equi, but without a history of respiratory disease in the preceding 4 months, and 2 horses with clinical purpura hemorrhagica. Serum IgA titers to culture supernatant protein antigen were highest in recently infected horses (P less than 0.001). Serial determinations of antibody titers in the horses with purpura showed that IgG antibodies to both S. equi M-like protein and culture supernatant protein antigens were undetectable initially, but later rose coincidental with clinical recovery from the disease. Possible mechanisms for these findings are discussed.

Animals↗