David T. Imagawa

Measles antibodies in multiple sclerosis.

Summary Examination of the sera of patients with multiple sclerosis by neutralization and complement-fixation tests revealed slightly higher antibody titers to measles virus than control subjects. The cerebral spinal fluid of patients with multiple sclerosis showed measurable antibody titers to measles virus in over 75% of the cases tested, whereas control subjects have shown no evidence of antibodies. The finding of elevated measles antibodies in the serum and spinal fluid of patients with MS does not imply or indicate a direct relationship but warrants continuing investigation.

Immunological Relationship Between Measles and Distemper Viruses.

Summary In tissue culture studies, the Edmonston strain of measles virus was neutralized by distemper antiserum prepared in ferrets with the egg-adapted and mouse-adapted strains of distemper virus. All normal ferret sera failed to show any neutralization of measles virus. In animal studies, ferrets immunized with measles virus and subsequently challenged with virulent distemper virus showed some evidence of protection as revealed by prolonged incubation periods, modified illnesses and survivals. The mouse-adapted distemper virus was completely neutralized by measles antiserum prepared in ferrets, whereas, normal serum failed to show any neutralization. Mouse-adapted distemper virus was also neutralized by human measles convalescent sera. These results suggest that common antigenic components are shared by the viruses of measles and distemper.

Importance of Medium in Demonstrating Penicillin Tolerance by Group B Streptococci

A total of 30 clinical isolates of group B streptococci were studied for penicillin tolerance in vitro. Minimal inhibitory and bactericidal concentrations of penicillin were determined simultaneously in three test media which have been used for group B streptococci, tryptose phosphate, Mueller-Hinton, and Todd-Hewitt broths, using a logarithmic-phase inoculum of 105 colony-forming units per ml. Minimal inhibitory concentrations in the three media did not differ significantly. However, minimal bactericidal concentrations were significantly higher in tryptose phosphate broth (mean, 1.04 μg/ml) than in Mueller-Hinton broth (0.22 μg/ml) or Todd-Hewitt broth (0.15 μg/ml). Similarly, ratios of minimal bactericidal to minimal inhibitory concentrations were significantly greater in tryptose phosphate broth than in Mueller-Hinton or Todd-Hewitt broth. After incubation in tryptose phosphate broth for an additional 24 h, the minimal bactericidal concentration consistently fell to levels which were only twice or equal to the minimal inhibitory concentration. This study illustrates the importance of the medium in the demonstration of penicillin tolerance and of controlling laboratory variables in the susceptibility testing of group B streptococci with penicillin.

Mechanism of Persistence with Canine Distemper Virus: Difference between a Laboratory Strain and an Isolate from a Dog with Chronic Neurological Disease

The mechanism of persistence in culture was different with canine distemper virus (CDV) isolated from a dog with chronic neurological disease (ODE; old dog encephalitis) compared to a laboratory strain (CDV/Ond). CDV/Ond persistence was achieved after seven undiluted passages while CDV/ODE-8, the recent isolate, showed immediate persistence in Vero cells. Both persistent infections resisted challenge with lytic CDV/Ond but not with unrelated vesicular stomatitis virus. The medium from CDV/Ond infection showed interference, whereas the medium from CDV/ODE-8 infection did not. Ultracentrifugation of the CDV/Ond supernatant effectively removed the defective interfering (DI) particles. Fluorescent microscopy showed the presence of CDV antigen in the cytoplasm of both types of persistently infected cells. By electron microscopy, 1% of the CDV/Ond cells and 23% of the CDV/ODE-8 cells showed distemper viral nucleocapsids. Persistence of CDV/Ond appears to be due to classical DI particles, whereas persistence of CDV/ODE-8 appears to be due to cell-associated particles. The persistence of CDV in dogs with ODE may be due to this cell-associated phenomenon.

Teratogenic Effects of Herpes Simplex, Vaccinia, Influenza - A (NWS), and Distemper Virus Infections on Early Chick Embryos.∗†:

Summary Herpes simplex, vaccinia and influenza-A (XWS) viruses produced teratogenic and lethal effects in the early chick embryo. The primary teratogenic effects of all 3 viruses were micrencephaly and axial flexion, but minor characteristic differences could be detected in embryos infected with each of these agents. Distemper virus failed to produce any gross embryologic changes, although its injection led to the development of ulcerative lesions on the C - A membrane and death of the embryo.

Propagation of rinderpest virus in suckling mice and its comparison to murine adapted strains of measles and distemper.

Tissue culture rinderpest virus was propagated in suckling mice through 16 serial intracerebral passages. The virus produced a lethal infection in mice 4–6 days following inoculation. The incubation period decreased progressively from 14 days to 4 days, and the mortality gradually increased until 100% was reached on the 6th passage. The LD50 titer of the infected brain material also gradually increased with passage and has remained relatively constant after the 5th passage ranging between 102.8 and 103.8 per 0.01 ml. The identity of the mouse propagated virus was unequivocally established by serum neutralization tests in suckling mice and cell cultures, and complement fixation tests employing infected mouse brains as antigens. Further identification was made by successful immunization of rabbits. Various properties of the rinderpest, measles and distemper viruses which were adapted to suckling mice in our laboratory were compared. These data indicate many similar properties but also minor differences among these mouse adapted viruses.

Failure of hypothalamic tissue to reinitiate thyrotropin production by mouse pituitaries in tissue culture.

Summary Contrary to Guillemins findings regarding the reinitiation of corticotropin production by pituitary explants in the presence of hypothalamic tissue, no thyrotropin was produced by mouse pituitary explants even after addition of growing hypothalamic tissue. Since the assay procedures employed would have detected 3 mU of thyrotropin, less than 4% of the original thyrotropin content of the explants was produced per week.

Neutralization of Teratogenic and Lethal Effects of Influenza-A Virus in Chick Embryos.

Conclusions Specific immune serum will protect the 48-hour chick embryo from the teratogenic and lethal effects produced by in fection with influenza-A virus. Inasmuch as antiserum can neutralize these effects completely in vitro and to a lesser extent in ovo this study provides serological evidence to implicate the virus as the cause of the syndrome described.

Serum neutralization of distemper virus in chick embryos.

Summary Virus-neutralization tests were carried out in embryonated hens eggs employing the egg-adapted distemper virus and various samples of serum. Ferrets whose sera contained no demonstrable antibody at 1:40 dilution all succumbed to 100 MLD of ferret distemper virus, whereas ferrets showing antibody titer to 1:640 dilution of serum all survived the same challenge dose. The data presented demonstrate that the results of serum-neutralization tests in chick embryos have a definite correlation with ferret protection tests. Human gamma globulin and some samples of human serum have neutralizing substances in titers as high as those known to exist in immune ferret serum. On the other hand, samples of serum from normal premature infants did not show any neutralizing substances in 1:40 dilution of the serum.

Measles virus: induced transfer of biological properties.

Neurotropic mouse measles virus (MMV), lethal for suckling mice, infects HeLa cultures with cytopathic effect but no cell-free virus is released. Edmonston strain (Edm), non-pathogenic for suckling mice, infects HeLa cultures with cytopathic effect and release of cell-free virus. Simultaneous, or sequential, infection of cell culture with MMV followed by Edm results in release of cell-free virus pathogenic for suckling mice as long as 35 days after mixed infection. The product is more like a heterozygote or phenotypic mix than a stable genetic recombinant. Rescue of MMV from cell culture by means of Edm is a model for recovery of incomplete virus which may be applied to other agents.