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Biomedical subjects

R C Kennedy

Publications and source records attributed to R C Kennedy.

At least 163 records · Page 9Linked to original sources

Royal pastel mink respond variously to inoculation with Aleutian disease virus of low virulence.

Information was sought on the varied responses of royal pastel mink (a non-Aleutian genotype) to Aleutian disease virus of low virulence. Thus, of 20 yearling female pastel mink inoculated subcutaneously with a large amount of the Pullman strain of Aleutian disease virus, only 3 succumbed to the disease. Of the other 17 mink, 3 had neither viremia nor a rise in level of serum gamma globulin during the 24 weeks after inoculation. The other 14 mink were viremic for variable periods during the first 12 weeks. In only five mink was the viremia accompanied by elevated levels of serum gamma globulin, usually from week 8 on. Of the 16 subclinically infected mink that did not succumb to intercurrent disease and otherwise remained healthy, 9 were examined at 19 to 31 months for persisting virus. In only one mink, small amounts were detected in the mesenteric lymph node and spleen nearly 28 months after inoculation. The other seven mink that survived the infection were not protected when challenged 31 months later with a small amount of the highly virulent Utah-1 strain. Even though still poorly understood, these varied responses of the royal pastel mink to infection with Aleutian disease virus of low virulence have important pathogenetic and epidemiological implications.

Aleutian Mink Disease↗

Antiidiotype modulation of herpes simplex virus infection leading to increased pathogenicity.

Antiidiotype reagents that recognize idiotypic determinants associated with the combining site of monoclonal antibodies to herpes simplex virus type 2 ( HSV2 ) were used to manipulate the immune response to HSV2 in BALB/c mice. The injection of antiidiotype antibodies into mice before challenge with a 50% lethal dose of HSV2 resulted in a shorter survival time than that of mice receiving either preimmune rabbit immunoglobulin G or antiidiotype reagents against hepatitis B surface antigen before HSV2 challenge. These findings indicate that the immune response to HSV2 in mice can be modulated through idiotype- antiidiotype networks, thereby increasing the pathogenicity of HSV2 infections.

Animals↗

Immune response to hepatitis B surface antigen: enhancement by prior injection of antibodies to the idiotype.

Anti-idiotype reagents that recognize a common idiotype associated with the combining site of antibodies to hepatitis B surface antigen (anti-HBs) were used to manipulate the immune response to hepatitis B surface antigen in BALB/c mice. The injection of antibodies to the idiotype before antigenic stimulation resulted in an increase in the number of cells secreting immunoglobulin M antibodies to hepatitis B surface antigen. Anti-HBs-secreting cells were also induced by administration of antibodies to the idiotype without subsequent antigen exposure. These findings indicate that the immune response to hepatitis B surface antigen in mice is regulated through an idiotype-anti-idiotype network.

Animals↗

Detection of interspecies idiotypic cross-reactions associated with antibodies to hepatitis B surface antigen.

A common idiotype was defined by a rabbit anti-idiotypic antiserum generated against human antibodies to hepatitis B surface antigen (anti-HBs). This idiotype was detected in anti-HBs from eight different individuals who had been previously infected with hepatitis B virus and is referred to as the CHBs idiotype. The CHBs idiotype was also identified in sera from rabbits, mice, guinea pigs, swine, goats and chimpanzees that had been immunized with hepatitis B surface antigen (HBsAg). Expression of the CHBs idiotype in sera from other species was associated with anti-HBs molecules. These results suggested that variable-region genes responsible for the CHBs idiotype have been conserved through long periods of evolution. It was noteworthy that the CHBs idiotype was not detected in the sera of a nonmammalian species, chickens, that had been successfully immunized with HBsAg.

Animals↗

Production and characterization of anti-idiotype reagents for the analysis of viral antigen systems.

Anti-idiotype reagents have been used recently in the characterization of a number of viral systems. These reagents provide a relatively new approach in viral immunology for the analysis of specific antibody molecules to viruses and their associated antigenic determinants. In this paper we report on the methodology for the generation and characterization of xenogeneic anti-idiotype antibodies in rabbits.

Animals↗

Comparative pathogenicity of four strains of Aleutian disease virus for pastel and sapphire mink.

Information was sought on the comparative pathogenicity of four North American strains (isolates) of Aleutian disease virus for royal pastel (a non-Aleutian genotype) and sapphire (an Aleutian genotype) mink. The four strains (Utah-1, Ontario [Canada], Montana, and Pullman [Washington]), all of mink origin, were inoculated intraperitoneally and intranasally in serial 10-fold dilutions. As indicated by the appearance of specific antibody (counterimmunoelectrophoresis test), all strains readily infected both color phases of mink, and all strains were equally pathogenic for sapphire mink. Not all strains, however, regularly caused Aleutian disease in pastel mink. Infection of pastel mink with the Utah-1 strain invariably led to fatal disease. Infection with the Ontario strain caused fatal disease nearly as often. The Pullman strain, by contrast, almost never caused disease in infected pastel mink. The pathogenicity of the Montana strain for this color phase was between these extremes. These findings emphasize the need to distinguish between infection and disease when mink are exposed to Aleutian disease virus. The distinction has important implications for understanding the natural history of Aleutian disease virus infection in ranch mink.

Aleutian Mink Disease↗

Biotin-avidin-amplified enzyme immunoassay for detection of herpes simplex virus antigen in clinical specimens.

A biotin-avidin-amplified enzyme-linked immunosorbent assay (B-A ELISA) has been developed to detect herpes simplex virus type 1 (HSV-1) and HSV-2 antigens in clinical specimens. The test was designed as a solid-phase, double-antibody, sandwich assay in which plates were coated with a polyclonal rabbit immunoglobulin G anti-HSV reagent, and the sandwich antibody was a biotin-labeled mouse immunoglobulin M monoclonal antibody that reacts with a common antigen associated with HSV-1 and HSV-2. The test can be completed in 4 h if antibody-coated plates are available. The detection limit of the B-A ELISA, determined by titration of virus stocks, was found to be approximately 90 PFU or 6 X 10(3) physical particles of either HSV-1 or HSV-2 per 50 microliter of virus stock. The following results were obtained in a study in which swabs were taken from a variety of lesions and assayed for infectivity in tissue culture and by B-A ELISA. Of 421 suspected HSV lesions tested, 69 were positive by both tests and 159 were negative by both tests. A total of 122 were positive by B-A ELISA but negative for infectivity. Seventy-one were negative by B-A ELISA but contained infectious virus. The HSV specificity of the assay was substantiated by partial blocking of reactivity with rabbit immunoglobulin G anti-HSV and by the absence of reactivity with a nonspecific biotin-labeled mouse immunoglobulin M monoclonal antibody.

Antigens, Viral↗

Characterization of anti-hepatitis B surface antigen monoclonal antibodies.

17 monoclonal antibodies generated against purified hepatitis B surface antigen (HBsAg), subtype ayw, were characterized by solid-phase radioimmunoassays. Eleven of these antibodies had specificity against the group-specific alpha determinant of HBsAg, two demonstrated antibody activity against the w HBsAg subtype, one against human serum albumin, and three against human IgG. All monoclonal antibodies were of the IgG class.

Antibodies, Monoclonal↗

Common idiotypic determinant associated with human antibodies to hepatitis B surface antigen.

Anti-Id antisera generated to purified anti-HBs isolated from two different individuals recognized a common idiotype. This idiotype was detected in purified anti-Hbs preparations from three individuals and also in anti-HBs-positive sera obtained from six hemophilic patients. The ability of both HBsAg and a virus-derived HBsAg native polypeptide to inhibit the idiotype-anti-idiotype reaction suggested that the anti-HBs idiotype was associated with the antibody-combining site.

Antibodies, Viral↗

Characteristics of a shared idiotype by two IgM anti-herpes simplex virus monoclonal antibodies that recognize different determinants.

Two IgM monoclonal antibodies (McAb) that recognized distinct antigenic determinants of herpes simplex virus type 2 (HSV2) were shown to share idiotypes. Seven other IgM McAb generated to either HSV2 or the major envelope glycoprotein of HSV2, VP119, did not express this shared idiotype. The idiotypic determinants were associated with the antibody-combining site, because HSV2 inhibited the idiotype-anti-idiotype reactions. Anti-HSV2 sera raised in BALB/c mice also expressed the idiotype shared by the two anti-HSV2 McAb.

Animals↗

Epitopes associated with a synthetic hepatitis B surface antigen peptide.

A synthetic peptide (SP1), corresponding to the amino acid residues 122 through 137 of the major polypeptide derived from hepatitis B surface antigen (HBsAg), subtype ayw, was analyzed for the presence of the major epitopes of HBsAg. Both a cyclic form, produced by introduction of an intrachain disulfide bond, and a linear form of the peptide were characterized. A panel of monoclonal antibodies with defined specificity for the cross-reactive group a antigenic determinant(s) and for the y and w subtype specificities was used for this analysis. The cyclic, but not the linear, form of SP1 reacted with five of 14 anti-a monoclonal antibodies, demonstrating that the cyclic peptide contains a conformation-dependent a epitope. Only one anti-a antibody was found to react with both cyclic and linear forms of SP1. Because SP1 failed to react with the remaining 8 anti-a monoclonal antibodies, it was concluded that the a antigenic reactivity associated with HBsAg contains an additional epitope(s) unrelated to that expressed on SP1. Both cyclic and linear SP1 reacted with three of three anti-y monoclonal antibodies, indicating that a sequential y epitope is also present on SP1; no w reactivity was detected. Analysis of the idiotypes associated with the monoclonal antibodies showed those that combined with cyclic SP1 also inhibited the binding of a common human anti-HBs (CHBs) idiotype with its rabbit anti-idiotype serum, whereas a monoclonal antibody that did not react with the cyclic SP1 epitope failed to inhibit the CHBs idiotype-anti-idiotype reaction. Thus, the conformational a epitope present on cyclic SP1 appears to contain the predominant epitope recognized by humans in response to a natural HBV infection.

Animals↗

Natural infection of Suffolk sheep with scrapie virus.

A better understanding of the infectious process in scrapie was sought by studying the temporal distribution of virus in naturally infected Suffolk sheep. Virus was detected (by mouse inoculation) first in lymphatic tissues and intestine of clinically normal lambs (age, 10-14 months). Titers were generally low. Infection of the central nervous system was first detected in a 25-month-old clinically normal sheep whose nonneural tissues had moderate amounts of virus. In sheep affected with scrapie, similar amounts in nonneural tissues accompanied high concentrations in the central nervous system, notably in sites of severest neurohistologic changes. No virus was found in clinically normal high-risk sheep 54 to 104 months old. The early appearance of virus in tonsil, retropharyngeal and mesenteric-portal lymph nodes, and intestine suggests that primary infection occurs by way of the alimentary tract, either prenatally from virus in amniotic fluid or postnatally from virus in a contaminated environment.

Animals↗

Brain tissue from persons dying of Creutzfeldt-Jakob disease causes scrapie-like encephalopathy in goats.

Two goats became affected with an encephalopathy indistinguishable from scrapie 43 months after they were inoculated intracerebrally with 10% suspensions of brain from two persons dying of Creutzfeldt-Jakob disease. Although this observation does not establish the common identity of Creutzfeldt-Jakob disease virus and scrapie virus, it is thought to provide strong evidence of a close etiological relationship between the two diseases.

Aged↗

Virologic and neurohistologic findings in dairy goats affected with natural scrapie.

Virologic and neurohistologic findings in three dairy goats that became affected with scrapie while living with naturally infected Suffolk sheep were essentially like those in affected sheep. Virus, detected by mouse inoculation, was widespread in non-neural sites, particularly in lymphatic tissues and intestine. Im most sites, titers of virus ranged from 3.0 to 3.5 log10 mouse intracerebral LD50/30 mg of tissue. Virus was in nervous tissue in much higher titer. Ranging from 5.1 to 5.8 log10, the highest mean titers were in the diencephalon, midbrain, medulla oblongata and cerebellar cortex--sites of the most severe histologic changes. Although these changes were like those in naturally affected Suffolk sheep, they differed somewhat from those in goats affected with the experimental disease. Spongiform alteration of neuropil was minimal, and the more rostral parts of the brain, such as corpus striatum, globus pallidus and septal area, had few changes. Concentrations and distribution of virus in non-neural tissues were consistent with the conclusion that scrapie virus no doubt can be maintained by contagion in a herd of goats living apart from infected sheep.

Animals↗