bluuebunny/crossref_metadata_2025 huggingface dataset:
Precipitation of measles virus proteins by immunoglobulin G fractions containing groups of oligoclonal bands isolated from sera of patients with subacute sclerosing panencephalitis
Authors: Lin F H , Mehta P D , Thormar H
Published: January 2020

Groups of oligoclonal immunoglobulin G (IgG) bands were isolated from sera of patients with subacute sclerosing panencephalitis by employing preparative isoelectric focusing. Six IgG fractions containing two to three oligoclonal bands with different isoelectric points were used to precipitate the proteins from Vero cells infected with measles virus. The results showed that all of the measles virus proteins except the M protein were precipitated by all of the IgG fractions and that the precipitation of viral proteins by the fractions containing groups of oligoclonal IgG showed slightly different patterns in some sera, whereas other sera showed no significant differences. The present study indicates that oligoclonal IgGs in subacute sclerosing panencephalitis sera are not specific to individual measles virus proteins.
Administration of a highly attenuated, live respiratory syncytial virus vaccine to adults and children
Authors: Wright P F , Belshe R B , Kim H W , Van Voris L P , Chanock R M
Published: January 2020

A highly attenuated respiratory syncytial virus (RSV) experimental vaccine, RSV ts-2, was sequentially evaluated in adults, seropositive children, and finally, fully susceptible seronegative children. The vaccine was administered intranasally in doses ranging from 10(5.2) to 10(6.3) PFU/ml. In both adults and children, the vaccine proved to be poorly infectious. Although poor infectivity would not have been predicted from tissue culture studies of RSV ts-2 growth, the human experience closely parallels the experience in a series of animal models, including the chimpanzee. The poor infectivity of this RSV vaccine virus preparation suggests that the postulated defect in the RSV ts-2 fusion protein may be important in determining in vivo infectivity of RSV.
Alteration in oligonucleotide fingerprint patterns of the viral genome in poliovirus type 2 isolated from paralytic patients
Authors: Yoneyama T , Hagiwara A , Hara M , Shimojo H
Published: January 2020

A close relationship was demonstrated by oligonucleotide fingerprinting between genomes of the poliovirus type 2 Sabin vaccine strain and recent isolates from paralytic cases associated with vaccination in Japan. The oligonucleotide maps of isolates from an agammaglobulinemic patient, who continued to excrete poliovirus type 2 for 3.5 years after the administration of oral vaccine, showed that the genomic alteration proceeded gradually, retaining the majority of the oligonucleotides characteristic of the vaccine strain for a long period, indicating vaccine origin for the isolates. The final isolate at month 41, however, lost the majority of these oligonucleotides. The heterologous antigenic relationship between the final isolate and the previous isolates was also observed. The serial alteration in electrophoretic mobility of the major structural proteins (VP1, VP2, and VP3) was observed throughout the excreting period. These results indicate that the population of the virus in this individual changed markedly during the last short period (about 3 months), in which the treatment with secretory immunoglobulin A was carried out. Genome comparisons in oligonucleotide maps show that some oligonucleotides in the genome of the vaccine strain are highly mutable after passage in humans.
Experimental infection and immune response of guinea pigs with varicella-zoster virus
Authors: Matsunaga Y , Yamanishi K , Takahashi M
Published: January 2020

An immune response (fluorescent antibody to membrane antigen) was detected in guinea pigs inoculated with varicella-zoster virus (VZV) adapted to guinea pig embryonic cells, including the Oka vaccine strain, even when inoculation was by an external route, i.e., nasal or corneal. Live or UV-inactivated virus having the same virus titer before irradiation was administered to guinea pigs by the corneal route, and antibody induction was detected only with live virus. The transmission of VZV from infected guinea pigs to noninfected ones was suggested by the appearance of antibody in the serum of the latter, who were kept in the same cage. The time course of the appearance of humoral and cellular immune responses in guinea pigs was examined by the fluorescent antibody to membrane antigen test and the skin reaction, with varicella antigen representing delayed-type hypersensitivity. When VZV was injected subcutaneously, skin reaction appeared as early as 4 days after inoculation, which preceded the appearance of detectable antibody by 2 to 6 days. In in vitro studies, the Oka vaccine showed a higher adsorption rate and better growth in guinea pig embryonic cells than did other wild-type strains when assayed by the infectious center assay. These results suggest that a system of VZV adapted to guinea pig cells and guinea pigs provides a good animal experimental model for immunological study of VZV infection.
Virus-specific antibodies in sera from patients with genital herpes simplex virus infection
Authors: Zweerink H J , Corey L
Published: January 2020

Virus-specific antibodies against a number of herpes simplex virus type 2 antigens were determined by radioimmunoprecipitation assays in sequential serum samples obtained from 12 patients with initial genital herpes simplex virus infection. The progressive appearance of antibodies to virus-specific antigens was observed; antibodies against a 130,000-molecular-weight glycoprotein complex appeared first, followed by antibodies against the major nucleocapsid polypeptide and then antibodies against a number of other viral antigens, including a polypeptide with a molecular weight of 62,000. Patients who developed a wide variety of antibodies to viral polypeptides shortly after resolution of their initial episode seemed to experience more severe initial infections and more recurrences than did those who reacted poorly with these virus-specific antigens. This was most apparent with respect to antibodies to virus-specific polypeptides with molecular weights between 30,000 and 43,000. Antibody specificity did not change during the course of follow-up regardless of whether serum samples were taken shortly before, during, or after recurrent episodes. Glycoprotein-specific antibodies were quantitated with the purified 130,000-molecular-weight glycoprotein material. No significant fluctuations in these antibody titers were observed before or after recurrences of the disease.
Toxic effect of human polymorphonuclear leukocytes on Chlamydia trachomatis
Authors: Yong E C , Klebanoff S J , Kuo C C
Published: January 2020

The effect of human polymorphonuclear leukocytes (PMNs) on Chlamydia trachomatis was studied. Both trachoma (B/TW-5/OT) and lymphogranuloma venereum (L2/434/Bu) biotypes were rapidly inactivated by exposure to human PMNs. A decrease of 3 to 3.5 logs in viable count was observed after 60 min of incubation at a chlamydia-to-PMN ratio of 1:10. Both chlamydial biotypes were also rapidly inactivated by the cell-free myeloperoxidase-H2O2-halide system. A decrease in infectivity titer of 4 to 5 logs for TW-5 and complete inactivation of 434 were seen after 30 min of incubation. The microbicidal effect was prevented by the deletion of each component of the system or by the addition of the peroxidase inhibitors cyanide or azide. PMNs from myeloperoxidase-deficient patients inactivated chlamydiae normally, whereas PMNs from patients with chronic granulomatous disease, although strongly chlamydicidal, were less effective than normal PMNs in the activation of TW-5 (2-log drop in viable organisms versus a 3 to 3.5-log drop). The chlamydicidal activity of PMNs from patients with chronic granulomatous disease and normal PMNs were comparable against the 434 biotype. These studies suggest that the myeloperoxidase system, or indeed oxygen-dependent antimicrobial systems, are not essential for the chlamydicidal activity of PMNs.
Gonococcal strains from homosexual men have outer membranes with reduced permeability to hydrophobic molecules
Authors: Morse S A , Lysko P G , McFarland L , Knapp J S , Sandstrom E , Critchlow C , Holmes K K
Published: January 2020

Loci designated penA, penB, and mtr contribute additively to penicillin G resistance in Neisseria gonorrhoeae; the mtr locus also confers resistance to hydrophobic dyes, detergents, and antibiotics, env mutations suppress the phenotypic expression of mtr and penB and are responsible for increased sensitivity to various hydrophobic molecules. We postulated that the host environment is important in the selection of gonococcal strains with these particular outer membrane phenotypes. Thus, mtr strains should predominate in environments that are high in hydrophobic molecules. To test this hypothesis we determined the outer membrane phenotype of 152 strains of N. gonorrhoeae. Rectal and urethral isolates from 58 homosexual men, urethral isolates from 55 heterosexual men, and cervical and rectal isolates from 39 heterosexual women were used in this study. Strains from 43 of the homosexual men were matched with those from heterosexual men with respect to auxotype and year and season of isolation. Cell envelope phenotype was determined for each strain on the basis of its resistance to various hydrophobic compounds. The identity of mtr strains was confirmed by genetic transformation. Among the matched pairs, mtr strains were significantly more prevalent among isolates from homosexual men than among those from heterosexual men (P = 0.03). Serogrouping by coagglutination demonstrated that 17 of 19 mtr strains versus 76 of 131 non-mtr strains belonged to coagglutination group WII (P = 0.01). Coagglutination group WII strains were also associated with homosexuality (P = 0.02). Gonococci were also tested for resistance to fecal lipids, mtr strains were more resistant to growth inhibition by fecal lipids than were non-mtr strains.
In vitro lymphocyte blastogenic responses and titers of humoral antibodies from periodontitis patients to oral spirochete isolates
Authors: Mangan D F , Laughon B E , Bower B , Lopatin D E
Published: January 2020

Humoral antibodies and in vitro blastogenic responses of patients with moderate to advanced periodontitis and of orally healthy (control) individuals to 11 spirochetes were assayed. Eight isolates of Treponema denticola, two isolates of T. vincentii, and one isolate of T. phagedenis were grown anaerobically, sonicated, and centrifuged to remove cellular debris. The blastogenic responses of peripheral blood lymphocytes were measured by [3H]-thymidine uptake. Antibody titers (immunoglobulins A, G, and M) to the spirochetes were measured with the micro-enzyme-linked immunosorbent assay. Dark-field microscopic enumeration of spirochetes was made from subgingival plaque. Spirochetes comprised 20% of the total number of microorganisms seen in plaque from the patients, whereas no spirochetes were seen in plaque from the controls. The blastogenic responses to the spirochetes were not statistically different (P greater than 0.05) between patients and controls. The immunoglobulin G and M antibody titers of the patients were generally lower than the titers of the controls, but the differences were rarely statistically significant. In contrast, the patients possessed significantly higher immunoglobulin A titers to seven spirochetes (T. denticola). No correlation was found between the percentage of spirochetes in the plaque sample and the blastogenic responses or titers of antibodies from an individual to the 11 spirochetes.
Immunoglobulin M responses to the Norwalk virus of gastroenteritis
Authors: Cukor G , Nowak N A , Blacklow N R
Published: January 2020

Eighty-seven serum specimens from 20 human subjects experimentally inoculated one or more times with Norwalk virus were quantitatively examined for virus-specific immunoglobulin M (IgM). A sensitive and specific radioimmunoassay for anti-Norwalk virus blocking activity was applied to whole serum and to separate IgM and IgG fractions obtained by sucrose density gradient ultracentrifugation. The peak IgM response occurred at about 2 weeks after illness, but IgM was detectable at lower titers for up to 21 weeks after infection. The IgM response was seen in volunteers who became ill, whether or not prechallenge total serum antibody was present. On long-term (27 to 42 months) rechallenge, volunteers who were previously ill and had produced IgM antibody again developed illness, and a secondary IgM response greater than the first was detected. Inoculated volunteers who did not develop illness, as well as previously ill volunteers on short-term rechallenge (4 to 14 weeks), usually failed to generate an IgM response, whether or not an IgG response had occurred. In ill subjects, the rise in IgM and IgG occurred concomitantly. Virus-specific IgM is not necessarily indicative of primary infection with Norwalk agent inasmuch as reinfection produces an enhancement of the IgM response. Furthermore, Norwalk-specific IgM responses do not appear to be associated with subclinical illness.
Characterization of the immune response in subcutaneous chambers of guinea pigs immunized with a ribosomal preparation from Neisseria gonorrhoeae
Authors: Wannemuehler M J , Miller R D , Cooper M D
Published: January 2020

Immunization of guinea pigs with ribosomal preparations has been previously shown to be protective against chamber infection with Neisseria gonorrhoeae, and this protection could be correlated with the presence of serum bactericidal antibody. Analysis of the chamber fluids from ribosome-immunized and nonimmunized guinea pigs has demonstrated that the chamber fluid may accurately reflect serum antibody levels and proteins. At least one major population of antiribosomal antibodies is present in both immune serum and chamber fluid as revealed by lines of identity between these components. Antibody- and complement-mediated bactericidal assays revealed that matched chamber fluids and sera from immune animals had comparable bactericidal titers. These results suggest that the antibody-complement-mediated bactericidal activity plays a major role in the protection against N. gonorrhoeae infection. Protection could not be explained on the basis of the cellular components of the inflammatory response since both immune and nonimmune chambers had comparable increases in polymorphonuclear neutrophils, monocytes, and lymphocytes after challenge.
Development of antibody-dependent cell-mediated cytotoxicity in the respiratory tract after natural infection with respiratory syncytial virus
Authors: Kaul T N , Welliver R C , Ogra P L
Published: January 2020

Antibody-dependent cell-mediated cytotoxicity (ADCC) was measured in nasopharyngeal secretions collected from 42 infants and young children at various intervals after primary or secondary infection with respiratory syncytial virus. ADCC was determined by specific immune release of 51Cr from respiratory syncytial virus-infected HEp-2 cell culture monolayers, with lymphocytes from adult volunteers as effector cells. Specific ADCC responses in nasopharyngeal secretions after primary infection were observed as early as 3 days after the onset of clinical symptoms, and peak activity was observed 14 to 29 days after the onset of illness. ADCC responses after reinfection were significantly greater in both the acute and convalescent phases (P less than 0.05) than were ADCC responses after primary infection. ADCC in secretions was mediated primarily by the immunoglobulin G isotype of respiratory syncytial virus antibody.
Humoral immune response to oral microorganisms in periodontitis
Authors: Doty S L , Lopatin D E , Syed S A , Smith F N
Published: January 2020

Serum antibody titers from patients with periodontitis were compared with those from periodontally healthy subjects. With the micro-enzyme-linked immunosorbent assay, immunoglobulin G (IgG), IgA, and IgM antibody titers to isolates of Streptococcus sanguis, Actinomyces viscosus, Bacteroides gingivalis, Bacteroides melaninogenicus subsp. intermedius, Bacteroides gingivalis, Bacteroides melaninogenicus subsp. intermedius, Bacteroides ochraceus, and Fusobacterium nucleation were determined. Antibody titers of the IgG and IgA classes to B. melaninogenicus, B. ochraceus, F. nucleatum, and S. sanguis were found to be significantly higher in the controls than in the patients. No correlations were found with serum IgM titers. These findings indicate that periodonitis may be associated with depressed antibacterial serum antibody titers of the IgG and IgA classes.
Temperature-inducible outer membrane protein of Yersinia pseudotuberculosis and Yersinia enterocolitica is associated with the virulence plasmid
Authors: Bölin I , Norlander L , Wolf-Watz H
Published: January 2020

A strain of Yersinia pseudotuberculosis which harbors a 63-kilobase plasmid was found to cause a lethal infection in Swiss albino mice. The rate of infection paralleled the ability of the pathogenic organism to attach to a monolayer of HeLa cells. One novel outer membrane protein (protein 1) with a molecular weight of 140,000 was found to be associated with the possession of the 63-kilobase plasmid not at 26 degrees C, and expression was moderately affected by the concentration of calcium in the growth medium. Moreover, it was found that synthesis of protein 1 associated outer membrane protein showing similar properties was also found to be expressed in plasmid-containing strains of Yersinia enterocolitica. The properties of protein 1 indicate that it could be identical to the previously described virulence W antigen.
Passive immunity in calf diarrhea: vaccination with K99 antigen of enterotoxigenic Escherichia coli and rotavirus
Authors: Snodgrass D R , Nagy L K , Sherwood D , Campbell I
Published: January 2020

Twenty-four pregnant cows were vaccinated intramuscularly with K99 extract from enterotoxigenic Escherichia coli and inactivated rotavirus as follows: six cows were injected with 2 ml of oil-adjuvanted vaccine; six cows were injected with 0.5 ml of oil-adjuvanted vaccine; six cows were injected with 4 ml of aluminum hydroxide-adjuvanted vaccine twice with a four-week interval; and six cows were unvaccinated as controls. Calves born to these cows were challenged with enterotoxigenic E. coli at 6 to 18 h after birth. Serum and milk antibodies to K99 and rotavirus in cows vaccinated with either dose of oil vaccine were significantly increased until at least 28 days after calving. In cows vaccinated with alhydrogel vaccine, there was a significant K99 antibody increase in serum and in colostrum but not in milk and a significant rotavirus antibody increase only in colostrum. Five of six calves born to unvaccinated cows developed enterotoxic colibacillosis after challenge, and all excreted the challenge strain of enterotoxigenic E. coli. None of the 18 calves in the three vaccinated groups developed clinical colibacillosis, and fecal excretion of the challenge organism was reduced. A combined enterotoxigenic E. coli-rotavirus vaccine may prove useful in preventing some outbreaks of calf diarrhea.
Lymphocyte-mediated immune cytotoxicity in dogs infected with virulent canine distemper virus
Authors: Appel M J , Shek W R , Summers B A
Published: January 2020

Immune lymphocyte-mediated cytotoxicity (ILMC) was evaluated in dogs after intranasal exposure to one of the following three virulent strains of canine distemper virus: Cornell A75/17, Ohio R252, and Snyder Hill. Cytotoxicity was tested with peripheral blood lymphocytes as effector cells and primary dog testicle cells that were matched for histocompatibility as target cells. A strong correlation was found between ILMC and the course of the infection. Dogs that succumbed to encephalitis with any of the strains had little or no ILMC, whereas dogs that recovered had the highest activity. In the intermediate range were dogs with a delayed or reduced ILMC which developed persistent but subclinical central nervous system infections. A significant difference in onset, peak, and duration of ILMC was observed in dogs infected with different strains of canine distemper virus. ILMC responses began at 14 days postinfection (p.i.), reached a peak at 21 to 28 days p.i., and returned to preinoculation levels by 63 to 70 days p.i. in canine distemper virus A75/17- and R252-infected dogs. In contrast, ILMC in canine distemper virus Snyder Hill-infected dogs began at 10 days p.i., peaked by 14 to 17 days p.i., and approached preinoculation levels by 28 days p.i. Antiviral immunity as measured by ILMC appears to be a critical factor in determining the outcome in canine distemper virus-infected hosts. Furthermore, for certain viral biotypes, a delayed ILMC response correlated with persistent infection of the central nervous system.
125I-peptide mapping of protein III isolated from four strains of Neisseria gonorrhoeae
Authors: Judd R C
Published: January 2020

Gonococcal outer-membrane protein I (PI) and PIII were isolated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis from reduced and unreduced whole-cell and outer-membrane lysates of four strains of nonpiliated (P-), transparent (O-) Neisseria gonorrhoeae. These proteins were radioiodinated and digested with alpha-chymotrypsin. The resultant 125I-peptides were then resolved by high-voltage thin-layer electrophoresis, followed by ascending thin-layer chromatography, and visualized by autoradiography. Results corroborated previous observations regarding the structural relationships of PIs having different apparent subunit molecular weights. All PIIIs had very similar apparent primary structures, regardless of the strain from which they were isolated, the source (i.e., whole cells or outer membranes), or the reduction state of the sodium dodecyl sulfate lysates. By the techniques used, it appeared that PIII is structurally similar in all of the gonococcal strains studied, even though each strain had structurally unique PIs.
Antigenic groupings of 90 rhinovirus serotypes
Authors: Cooney M K , Fox J P , Kenny G E
Published: January 2020

We have completed production in rabbits of potent antisera to the 90 classified rhinovirus serotypes by using methods previously described (M. K. Cooney and G. E. Kenny, Proc. Soc. Exp. Biol. Med. 133:645-650, 1970). Systematic testing by neutralization tests has revealed significant numbers of cross-relationships among rhinovirus types, some of which have already been reported. Herein, our observations are compared with cross-reactions reported in National Institutes of Health reference guinea pig antisera. Also, original rhinovirus isolates, representing serotypes known to be antigenically related to other rhinoviruses, were tested against rabbit antisera to the related serotypes. These tests revealed extensive antigenic variation among isolates identified as rhinovirus 12:78 or 36:58, which are reciprocally related pairs, 41, reciprocally related to 13, and 67, which is related to both 9 and 32. If the rhinovirus serotypes were grouped according to antigenic relationships, 50 types could be included in 16 groups.
Utilization of human respiratory secretions by mucoid Pseudomonas aeruginosa of cystic fibrosis origin
Authors: Ohman D E , Chakrabarty A M
Published: January 2020

Growth and exoproduct production were examined with sputum from patients with respiratory diseases serving as the growth substrate for mucoid strains of Pseudomonas aeruginosa isolated from cystic fibrosis (CF) patients. Mucoid strains are uniquely common to chronic respiratory infections of CF patients. The mucoid colonial morphology of P. aeruginosa is due to the biosynthesis of the exopolysaccharide alginate. Alginate-producing (Alg+) strains utilized CF sputum for growth and high yields of alginate; however, sputum from patients with other respiratory diseases produced comparable results. Analysis of CF sputum medium indicated that amino acids and small peptides were major substrates for P. aeruginosa in respiratory secretions. Cultures of Alg+ strains in CF sputum medium were inhibited in growth and reduced in alginate yields by a low concentration (1 mM) of D-mannose, suggesting therapeutic applications. The rates of growth of two Alg+ strains in CF sputum medium were found to be slightly lower compared with their respective spontaneous Alg- mutants, indicating that the mucoid phenotype does not enhance the ability of P. aeruginosa to utilize respiratory secretions. At all stages of growth in CF sputum medium, two Alg+ strains produced lower yields of protease than did their respective Alg- mutants. When seven Alg+ strains of CF origin were compared with their respective Alg- mutants, the Alg+ phenotype correlated with reduced yields of extracellular proteases. These data are consistent with the hypothesis that mucoid strains of P. aeruginosa are more suited to chronic rather than to acute respiratory infections in that reduced yields of proteases temper the level of damage to the lungs and result in a reduced infiltration of phagocytic cells.
Mediators of protection against lethal systemic vesicular stomatitis virus infection in hamsters: defective interfering particles, polyinosinate-polycytidylate, and interferon
Authors: Fultz P N , Shadduck J A , Kang C Y , Streilein J W
Published: January 2020

Homologous defective interfering (DI) particles protected adult Syrian hamsters against lethal systemic infection with vesicular stomatitis virus (VSV) serotype Indiana. The DI particles had to be biologically active, but did not have to be administered at the same inoculation site as the infectious virus. Serum and tissue levels of VSV postinoculation were significantly lower in DI-protected animals than in unprotected controls, suggesting that true autointerference was occurring. However, some aspects of protection also must be mediated through nonspecific mechanisms, since susceptible hamsters could be protected against VSV Indiana by coinjection with heterologous DI particles prepared from VSV serotype New Jersey or by simultaneous administration of polyinosinic acid-polycytidylic acid. By measuring serum levels of putative hamster interferon (type 1), we found that animals coinjected with VSV and DI particles or polyinosinic acid-polycytidylic acid produced significant levels of interferon. Since similarly high serum levels of interferon were measured in recipients of VSV alone (animals that eventually died from infection), there appeared to be no correlation between protection against lethal disease and induced levels of serum interferon. Instead, serum interferon levels correlated positively with amounts of VSV PFU found in serum and tissues of infected animals, the lowest levels being found in serum of animals protected with homologous DI particles. The data are consistent with the hypothesis that autointerference by DI particles as well as various host defense mechanisms (possibly including induction of interferon) participates in protecting hamsters against lethal VSV infection.
Nonspecific recruitment of lymphocytes in purified protein derivative-induced lymphocyte proliferative response of patients with tuberculosis
Authors: Tsuyuguchi I , Shiratsuchi H , Fujiwara H , Teraoka O
Published: January 2020

Peripheral blood lymphocytes (PBL) from tuberculosis patients were studied for their in vitro proliferative response stimulated with purified protein derivative (PPD)-tuberculin. Studies were designed to characterize the lymphocytes involved in the PPD-induced proliferation. PPD-responsive lymphocytes were eliminated in PBL by the procedure of cultivation of PBL with PPD in the presence of 5-bromodeoxyuridine and light illumination of the cultured cells. These PBL which lost PPD reactivity were no longer able to proliferate to PPD stimulation but were still capable of proliferation in the presence of both PPD and X-irradiated, autologous fresh PBL or upon addition of culture fluids from PPD-stimulated PBL. In addition, these nonspecifically activated lymphocytes released a soluble factor into the culture fluids which inhibited the migration of leukocytes. It was likely that large numbers of nonspecific T cells were induced to proliferate as a result of the presentation of specific T cells with the antigen PPD. It is suggested that a similar recruitment of lymphocytes by PPD-stimulated T cells takes place in vivo during the establishment of tuberculosis or antituberculous immunity or both.
Salmonella typhimurium infection in calves: delayed specific skin reactions directed against the O-antigenic polysaccharide chain
Authors: Robertsson J A , Svenson S B , Lindberg A A
Published: January 2020

Specific delayed skin reactions developed after intradermal injection of Salmonella typhimurium lipopolysaccharide in 12-week-old calves which had been orally infected with S. typhimurium 5 weeks earlier. Uninfected calves showed no delayed skin reactions. Skin biopsies from skin swellings showed a massive infiltration of mononuclear cells in the skin of infected calves but not in those of uninfected calves. Persistence of infection in infected calves was confirmed by isolation of S. typhimurium from fecal specimens. The delayed skin reactions could be shown to be specific and directed against the O-polysaccharide chain of the lipopolysaccharide since none of the lipopolysaccharide chain of the lipopolysaccharide since none of the lipopolysaccharide preparations from a rough mutant of S. typhimurium, two strains with different O-polysaccharide chains, or lipid A elicited skin reactivity. To cause a reaction, the O-polysaccharide had to be in a macromolecular complex, since skin swellings were seen only after injections of either O-polysaccharide chains cross-linked by 1,2,3,4-diepoxybutane or octasaccharides from the O chain covalently linked to a straight 12-carbon aliphatic chain forming an artificial glycolipid. Injection of the pure octasaccharides of O-polysaccharide chains failed to elicit delayed skin reactions.
Detection of Tissue Culture-Adapted Theiler's Virus RNA in Spinal Cord White Matter Cells Throughout Infection
Authors: Stroop William G. , Brahic Michel , Baringer J. Richard
Published: January 2020

The appearance of histological lesions and the localization of viral RNA in the central nervous system of mice infected with tissue culture-adapted Theiler's murine encephalomyelitis virus (WW strain) (TMEV-WW) was studied. Viral RNA was detected by autoradiography after in situ hybridization, using a
3
H-labeled DNA probe complementary to virion RNA, which was applied to deparaffinized sections of central nervous system tissues from infected mice. Subjacent histological sections of tissues were used to assess the location and extent of lesions. Lesions were first observed at 20 days post-inoculation and appeared to enlarge throughout infection. They consisted of infiltrates of mononuclear cells and lymphocytes in spinal cord white matter and leptomeninges; at 78 days post-inoculation severe necrotizing and demyelinative myelitis and gliosis were observed. In contrast to the pathogenesis of brain-derived TMEV-WW-infected mice, no lesions were found in the central nervous system gray matter of mice infected with tissue culture-adapted TMEV-WW at any time post-infection. Tissue culture-adapted viral RNA was found in the cells of spinal cord white matter throughout infection; only one neuron in close proximity to the injection site was found to contain viral RNA shortly after infection. At early times after infection, spinal cord white matter cells containing viral RNA were found before development of inflammatory lesions; at later days post-inoculation, positive cells were found within, at the periphery of, or at a distance from lesions. The number of infected cells and the amount of viral RNA per cell appeared to remain constant from 20 to 78 days post-inoculation despite the increasing intensity of the inflammatory response. The nearly exclusive spinal cord white matter tropism of tissue culture-adapted TMEV-WW appeared to directly correlate with the disease-inducing potential of this virus.
Pathogenesis of Lassa virus infection in guinea pigs
Authors: Jahrling P B , Smith S , Hesse R A , Rhoderick J B
Published: January 2020

A rodent model for human Lassa fever was developed which uses inbred (strain 13) and outbred (Hartley) guinea pigs. Strain 13 guinea pigs were uniformly susceptible to lethal infection by 2 or more PFU of Lassa virus strain Josiah. In contrast, no more than 30% of the Hartley guinea pigs died regardless of the virus dose. In lethally infected strain 13 guinea pigs, peak titers of virus (10(7) to 10(8) PFU) occurred in the spleen and lymph nodes at 8 to 9 days, in the salivary glands at 11 days, and in the lung at 14 to 16 days. Virus reached low titers (10(4) PFU) in the plasma and brain and intermediate titers in the liver, adrenal glands, kidney, pancreas, and heart. In moribund animals, the most consistent and severe histological lesion as an interstitial pneumonia. In contrast, the brain was only minimally involved. The immune response of lethally infected strain 13 guinea pigs, as measured by the indirect fluorescent antibody test, was detectable within 10 days of infection and was similar in timing and intensity to the fluorescent antibody test response of both lethally infected and surviving outbred animals. In contrast to the fluorescent antibody response, neutralizing antibody developed late in convalescence and was thus detected only in surviving outbred guinea pigs. The availability of a rodent model for human Lassa fever in uniformly susceptible strain 13 guinea pigs should facilitate detailed pathophysiological studies and efficacy testing of antiviral drugs, candidate vaccines, and immunotherapy regimens to develop control methods for this life-threatening disease in humans.
Strain-related differences in lysozyme sensitivity and extent of O-acetylation of gonococcal peptidoglycan
Authors: Rosenthal R S , Blundell J K , Perkins H R
Published: January 2020

Peptidoglycan from Neisseria gonorrhoeae RD5 was completely degraded by hen egg white lysozyme and was not extensively O-acetylated. In contrast, peptidoglycans from gonococcal strains FA19 and FA102 (a penicillin-resistant mutant derived from FA19), were markedly resistant to digestion by hen egg white lysozyme and were extensively O-acetylated.
Isolation and Characterization of Pneumolysin-Negative Mutants of
Streptococcus pneumoniae
Authors: Johnson Mary K. , Hamon David , Drew Gloria K.
Published: January 2020

Pneumolysin-negative mutants of
Streptococcus pneumoniae
were isolated after mutagenesis with ethyl methane sulfonate. Though totally devoid of pneumolysin, these strains produced alpha hemolysis on blood agar when incubated aerobically. It is concluded that the alpha hemolysis typical of pneumococci is unrelated to their pneumolysin content.
Immune response to lactate dehydrogenase-elevating virus: isolation of infectious virus-immunoglobulin G complexes and quantitation of specific antiviral immunoglobulin G response in wild-type and nude mice
Authors: Cafruny W A , Plagemann P G
Published: January 2020

Lactate dehydrogenase-elevating virus (LDV) causes a normally benign persistent infection of mice, resulting in a life-long viremia characterized by the presence of circulating infectious immune complexes, impaired clearance of certain enzymes from the blood, and modification of the host immune response to various heterologous antigens. In this study, we isolated infectious immunoglobulin G (IgG)-LDV complexes in the plasma of persistently infected mice by adsorption to and elution from protein A-Sepharose CL-4B. We found that practically all infectious LDV in the plasma of persistently infected mice is complexed to IgG. LDV infectivity in these complexes was partially neutralized, but could be reactivated by treatment with 2-mercaptoethanol. We also quantitated total plasma IgG and anti-LDV IgG in wild-type and nude Swiss and BALB/c mice as a function of the time after infection with LDV by radial immunodiffusion and an enzyme-linked immunosorbent assay, respectively. Total plasma IgG levels nearly doubled in BALB/c mice during 150 days of infection. IgG levels in uninfected nude mice were only 20% of those in uninfected BALB/c mice, but during infection with LDV increased to approximately those found in uninfected BALB/c mice. Anti-LDV IgG levels were almost as high in nude mice as in normal BALB/c mice. Isoelectric focusing of purified IgG from BALB/c mice showed that LDV infection resulted in the enhanced synthesis of all 16 normal IgG fractions that we could separate by this method, which suggests that LDV infection results in polyclonal activation of IgG-producing lymphocytes.
Evidence for an unconventional virus in mouse-adapted Creutzfeldt-Jakob disease
Authors: Kingsbury D T , Smeltzer D A , Amyx H L , Gibbs C J , Gajdusek D C
Published: January 2020

Homogenates of a human brain from a case of Creutzfeldt-Jakob disease and a homogenate of mouse brains from mouse passage 1 of the disease in mice contained no detectable conventional viruses. Both human material and mouse-passaged material were inoculated into nude mice, and the mouse-passaged material was also inoculated into eight different tissue culture lines. The tissue cultures showed no cytopathic changes or hemadsorption and failed to produce an increased amount of reverse transcriptase. The nude mice inoculated with human brain suspensions developed a disease identical to that in immunocompetent mice, with a nearly identical incubation period of 9 to 13 months. The incubation period of the disease in mice was under host genetic control and was, additionally, directly related to the inoculum size. The agent was resistant to 10% Formalin, 5% deoxycholate, 1% Triton X-100, and 5% glutaraldehyde; however, glutaraldehyde treatment resulted in a significant loss of infectivity. Approximately 1 log of infectivity was lost by heating brain suspensions to 80 degrees C for 15 min, with no additional loss upon further incubation up to 45 min. Heating at 100 degrees C for 15 min led to a 3-log loss of infectivity.
Parenteral Immunization with Live Respiratory Syncytial Virus Is Blocked in Seropositive Cotton Rats
Authors: Prince Gregory A. , Horswood Robert L. , Camargo Ena , Suffin Stephen C. , Chanock Robert M.
Published: January 2020

Seropositive cotton rats cannot be immunized by intramuscular inoculation of live respiratory syncytial virus. Passively administered antiserum was shown to effect the immunosuppression. By contrast, the presence of serum antibody did not block immunization by the intranasal route.
Evidence for the secretion of soluble peptidoglycans by clinical isolates of Staphylococcus aureus
Authors: Zeiger A R , Wong W , Chatterjee A N , Young F E , Tuazon C U
Published: January 2020

Four isolates of Staphylococcus aureus from patients with endocarditis and bacteremia were capable of secreting high-molecular-weight soluble peptidoglycans when grown in a minimal cell wall medium containing penicillin G. Vancomycin was not able to substitute for penicillin G in triggering this secretion. Secretion reflected de novo synthesis of soluble peptidoglycan and was strongly dependent on time of incubation (30 to 60 min), and number of bacteria (2 X 10(8) to 5 X 10(8) colony-forming units per ml), but not on penicillin G concentration (10 to 250 micrograms/ml). The incorporation of alanine into the peptidoglycans secreted in vitro by these isolates incubated in the presence of penicillin G under optimal conditions was variable. The least incorporation of alanine into peptidoglycan occurred with an isolate from a patient treated with nafcillin who had no detectable antipeptidoglycan titer.
Role of Ia Antigen Expression and Secretory Function of Accessory Cells in the Induction of Cytotoxic T Lymphocyte Responses Against Herpes Simplex Virus
Authors: Schmid D. Scott , Larsen Hal S. , Rouse Barry T.
Published: January 2020

Splenocytes from mice which have been primed in vivo with herpes simplex virus type 1 (HSV-1) can be restimulated in vitro with infectious or UV-inactivated HSV-1 to generate HSV-specific,
H-2
-restricted cytotoxic T lymphocytes (CTL). HSV-primed splenocytes which have been depleted of adherent cells by sequential incubation on plastic, nylon wool, and Sephadex G-10 are not able to respond with a CTL response when restimulated in vitro. A variety of Ia-positive and Ia-negative (Ia
+
and Ia
−
) cell populations were assessed for their ability to supply accessory cell functions to spleen cells which had been exhaustively depleted of adherent cells, as measured by the restoration of a CTL response to HSV-1. Of these, only those populations which included Ia
+
cells were capable of providing accessory cell function. The ineffective populations were devoid of Ia antigens, except for B lymphocytes, which are Ia
+
and still incapable of serving as accessory cells. Splenic adherent cells and resident peritoneal cells were both proficient at restoring anti-HSV CTL responses, although splenic adherent cells were clearly superior at limiting cell numbers. Neither population was capable of accessory cell activity, however, if it was pretreated with anti-Ia antiserum plus complement or if anti-Ia serum was present during induction. Peritoneal cells lose virtually all of their membrane-associated Ia antigen after a brief period of in vitro culture (24 to 48 h). Cultured peritoneal cells, as well as P388D
1
cells (normally Ia
−
), can be induced to express Ia antigens within 48 h if they are cultured with concanavalin A-stimulated spleen cell supernatants. Ia
+
P388D
1
cells without the extraneous macrophage factor are not able to restore CTL responsiveness to HSV-1 in vitro, whereas Ia
+
cultured macrophages are fully competent accessory cells. When Ia
+
P388D
1
cells were supplemented with the macrophage-derived soluble factor interleukin 1, they displayed a modest, but significant, capacity to restore secondary anti-HSV CTL responses. In addition, glutaraldehyde-fixed, HSV-1-infected Ia
+
peritoneal cells, which could not restore the CTL response alone, were capable of providing accessory cell function if extraneous interleukin 1 was provided. In contrast, Ia
−
cultured peritoneal cells, Ia
−
P388D
1
cells, and various other Ia
−
cell lines were unable to participate in the generation of CTL even in the presence of interleukin 1. The adherent cell population would therefore appear to be making at least two essential contributions to the process of CTL development, namely, the secretion of interleukin 1 and the presentation of antigen in the context of membrane-associated Ia antigen.
Immunocompetence of chickens during early and tumorigenic stages of Rous-associated virus-1 infection
Authors: Fadly A M , Lee L F , Bacon L D
Published: January 2020

A study was designed to determine the effects of congenital infection with the Rous-associated virus-1 (RAV-1) on the immune function chickens during the early and late tumorigenic stages of infection. In another experiment, the effects of niridazole on the immune competence and the tumor incidence in chickens congenitally infected with RAV-1 were studied. Lymphocyte stimulation by phytohemagglutinin, the phytohemagglutinin skin test, the response to immunization with sheep erythrocytes and Brucella abortus, and histological evaluation of lymphoid organs were used to determine the immune competence in normal and infected chickens. Results indicated that both B- and T-cell immune functions during the early and late stages of RAV-1 infection were comparable to those of normal uninfected chickens. Administration of niridazole to congenitally infected chickens at 5 weeks of age for 7 or 21 days had no effect on the T-cell-mediated immunity; however, administration of the drug for 21 days eliminated lymphoma development. Unlike infection with other oncogenic viruses such as those causing Marek's disease and reticuloendotheliosis, infection with RAV-1 caused no detectable immunodepression during the early and late stages of infection.
Interaction of Mycoplasma hyopneumoniae with the porcine respiratory epithelium as observed by electron microscopy
Authors: Tajima M , Yagihashi T
Published: January 2020

An in vivo-passaged strain of Mycoplasma hyopneumoniae attained viability titers of 10(6) to 10(8) color-changing units per mg of tissue in pig lungs and caused gross and histological pulmonic lesions. Mycoplasmas were readily located in the lumina of the respiratory tract by electron microscopy. In sections of tissue fixed in glutaraldehyde-osmium, the organisms were found to possess many radial fibrils on the outer surface of the limiting membrane. These fibrils appeared to interconnect adjacent mycoplasmas and to extend between the organism and epithelial cell. Ruthenium red staining demonstrated a thick, dark layer of capsular material enveloping the entire mycoplasma cell. The capsular material was seen to bridge the space between the mycoplasma and host cell. The general morphology of the in vitro-passaged strains grown in broth medium was essentially similar to that of the in vivo-passaged strain. In these organisms, however, no long fibrils were seen, although a fuzzy layer was present outside the cell membrane. The ruthenium red-positive capsule was stained less intensely, and its width was only about one-half that observed for the in vivo-passaged strain. In negatively stained preparations, the cells had an outer fringe of amorphous material apparently corresponding to the fuzzy layer seen in thin sections. The in vitro-passaged strain grew poorly in pig lungs and lost its ability to produce gross pulmonic lesions. The organisms in the respiratory tract had a capsule much thinner than that of the in vivo-passaged strain.
Liberation of serotonin from rabbit blood platelets by bacterial cell walls and related compounds
Authors: Harada K , Kotani S , Takada H , Tsujimoto M , Hirachi Y , Kusumoto S , Shiba T , Kawata S , Yokogawa K , Nishimura H , Kitaura T , Nakajima T
Published: January 2020

A study was made on the activity of various bacterial cell walls and peptidoglycans to liberate serotonin from rabbit blood platelets. All of the test cell walls or peptidoglycans prepared from 27 strains of 21 bacterial species were shown to cause a marked release of serotonin, regardless of differences in types of peptidoglycan and non-peptidoglycan moieties and in some biological properties. The assay made with the water-soluble "digests" of Staphylococcus epidermidis cell wall peptidoglycans, which were prepared by use of appropriate enzymes, revealed that a polymer of peptidoglycan subunits (a disaccharide-stempeptide) was definitely active in the release of serotonin, but a structural unit monomer was inactive. Among a variety of synthetic muramylpeptides and their 6-O-acyl derivatives, only 6-O-(3-hydroxy-2-docosylhexacosanoyl)-N-acetylmuramyl-L-alanyl-D-isoglutaminyl- L-lysyl-D-alanine was found to hold a strong serotonin-liberating activity.
Plasmodium berghei malaria: blockage by immune complexes of macrophage receptors for opsonized plasmodia
Authors: Brown K M , Kreier J P
Published: January 2020

Immune complexes produced in vitro by mixing immune serum and soluble Plasmodium berghei antigens and immune complexes precipitated from serum of acutely infected rats blocked macrophage receptor sites for opsonized plasmodia. The immune complexes were precipitated from acute-phase serum, using polyethylene glycol, and their composition was determined by using a Raji cell immunofluorescence assay. The immune complexes contained immunoglobulin G (IgG), IgM, and malarial antigens. These results indicate that immune complexes in the serum of acutely infected animals may protect the plasmodia from the activities of macrophages.