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Biomedical subjects

H Koprowski

Publications and source records attributed to H Koprowski.

At least 397 records · Page 22Linked to original sources

Suppression of cell-mediated immunity by street rabies virus.

Mice lethally infected with street rabies virus failed to develop cytotoxic T cells specific for rabies virus-infected target cells, whereas high levels of cell-mediated cytotoxicity (CMC) were generated after nonfatal infection with the attenuated high egg passage (HEP) or ERA rabies virus strains. Furthermore concurrent infection with street, but not with HEP, rabies virus suppresses development of a primary (but not a secondary) CMC response specific for influenza virus. No cross-reactivity is found between effector T-cell populations from mice immunized with HEP or with influenza virus. It thus appears that street rabies virus, which is not known to replicate in the cells of immune system, induces some general defect in the primary CMC lymphocyte response, though restimulation of memory T-cell populations is unimpaired and there is no defect in antibody formation. Development of fatal rabies may reflect the operation of this selective immunosuppressive mechanism.

Animals↗

A new approach in specific, active immunotherapy.

A vaccinia virus-lysed autochthonous tumor cell vaccine (vaccinia oncolysate) is introduced as a new specific, active immunotherapeutic agent against human cancer. Mouse experiments showed the vaccine to be a safe and potent immune mechanism stimulator. Human experimentation was undertaken in the knowledge of relative safety of the components of the vaccine, i.e. vaccinia vaccine and lysed, autochthonous tumor cells. Vaccine-treated patients had advanced metastatic cancer but reacted to one or more common recall antigen skin tests. None of the 13 patients had untoward responses; 7/13 patients had classic delayed hypersensitivity reactions at the vaccine injection sites; and 2/7 patients with injection site reactions had significant reduction in tumor burden. These results indicate that this vaccine is a specific, active immune mechanism stimulator, and may prove to be a useful therapeutic agent in the treatment of human cancer.

Animals↗

Ultrastructural study of concanavalin-A binding to the surface of preimplantation mouse embryos.

Receptors for Con-A were labelled (using the peroxidase-diaminobenzidine technique) on the plasma membrane of unfertilized and fertilized mouse eggs, cleavage stage embryos, trophoblast and inner cell mass (ICM) of the blastocyst. Embryos were exposed to Con-A concentrations of 10 microgram/ml, 50 microgram/ml, or 1,000 microgram/ml and the lowest concentration was observed to be the most suitable for discerning differences between stages of embryonic development. On the surface of unfertilized and fertilized eggs and 2-cell embryos, reaction product appeared as a thin, discontinuous layer. The surface of 4- and 16-cell stage embryos had a thicker, continuous, although non-uniform, layer of the reaction product. On the surface of the cells of the late morula, and on the trophoblastic cells of the blastocyst, clustering of reaction product was observed. Cells of ICM of intact blastocyst were free of the reaction product, showing that either Con-A and/or peroxidase cannot penetrate tight junctions between trophoblastic cells. Reaction product in the form of a thin, uniform layer covered the free surface of the cells of the ICM after they had been isolated (using immunosurgery) and exposed to 50 microgram/ml of Con-A. The amount and distribution of Con-A receptors is discussed, along with their redistribution and mobility in relation to the agglutinability of preimplantation mouse embryos.

Animals↗

In vitro evidence of cell-mediated immunity after exposure of mice to both live and inactivated rabies virus.

Mice exposed to live or beta-propiolactone-inactivated rabies virus generated a strong, specific cell-mediated cytotoxic response which was generally maximal 6 days after inoculation. Release of 51Cr was apparently a function of immune thymus-derived lymphocytes (T cells) because it was abrogated by prior incubation of spleen cells with anti-thymus antiserum and complement but was undiminished by passage of spleen cells through nylon-wool columns. Cytotoxicity was always maximal for interactions in which thymus-derived cells and targets shared H-2 genes but, unlike the situation found in other assays of this type, considerable lysis of allogeneic, virus-infected target cells may also occur. Perhaps the most significant finding from these experiments is that an inactivated virus has been shown to stimulate a potent cytotoxic thymus-derived cell response. Manipulation of this experimental model may allow analysis of the antigens required for stimulation of cell-mediated immunity. A more practical consequence may be the development of more rational protocols for postexposure vaccination against rabies. Prior treatment of mice with antirabies antibody severely depressed the generation of cell-mediated immunity.

Animals↗

Tumorigenicity of simian virus 40-transformed human cells and mouse--human hybrids in nude mice.

Four different human cell lines transformed by simian virus 40 (SV40) were tested for their tumorigenicity in athymic nude mice. Two of these lines, W18Va2 and GM52VA, were found to be tumorigenic when inoculated at a concentration of 1 x 10(7) cells per mouse. The other two cell lines, LN-SV and GM54VA, were found to induce very small tumors only after the injection of approximately 1 x 10(8) cells per mouse. Somatic cell hybrids between either LN-SV or GM54VA SV40-transformed human cells and normal mouse peritoneal macrophages, which have retained the human chromosomes carrying the SV40 genome, were found to be much more tumorigenic than the SV40-transformed human cell parents. These experiments suggest that the genetic background in which the human chromosomes carrying the SV40 genome are present plays a role in the modulation of the expiration of malignancy.

Animals↗

Induction and biological properties of defective interfering particles of rabies virus.

A method for obtaining large quantities of defective interfering (DI) rabies virus particles that fulfill all the criteria delineated by Huang and Baltimore (1970) is described. The purified rabies DI virion was found to be much shorter (60 to 80 nm) than the complete virion (180 nm) and to have a viral genome of about half the size of normal rabies RNA but with all of the structural proteins of standard virions. Rabies DI virions were noninfectious for both cells in culture and for animals. As determined by in vitro and in vivo techniques, interference with the replication of standard virus was specific to rabies virus. The possible role of rabies DI virion in the pathogenicity of rabies virus infection and in the establishment of attenuated strains for use as live rabies vaccines is discussed.

Animals↗

Successful protection of humans exposed to rabies infection. Postexposure treatment with the new human diploid cell rabies vaccine and antirabies serum.

Forty-five persons severely bitten by rabid dogs and wolves in Iran were treated after exposure with a new rabies vaccine produced in cultures of human diploid cells. All except one also received one injection of rabies immune serum. This treatment, in contrast to past experience with other vaccines, resulted in protection of all individuals against rabies. Thus, almost a century after the postexposure treatment of humans was initiated, an effective tool for protecting man against rabies has finally been developed.

Adolescent↗

Circulating immune complexes in multiple sclerosis and other neurological diseases.

Circulating immune complexes were detected in 49% of sera from patients with multiple sclerosis, 45% of monosymptomatic optic neuritis, 45% of Guillain-Barré syndrome, and 15% of normal sera studied. The frequency of immune complexes in multiple-sclerosis sera was not correlated with the clinical status of the patients. Results with serial blood-samples were variable.

Antigen-Antibody Complex↗

Experimental parainfluenza type 1 virus-induced encephalopathy in adult mice. Pathogenesis of chronic degenerative changes in the CNS.

The pathogenicity of the 6/94 strain of parainfluenza type 1 virus, originally isolated from multiple sclerosis brain, was studied in adult mouse brains. Intracerebral inoculation of the virus caused mononuclear cell infiltration in the form of perivascular cuffing and a diffuse exudation into the parenchymal tissue, preferentially in cerebral white matter, that resulted in marked degeneration over a 90-day observation period. Immunofluorescent staining revealed viral antigen in the ependymal lining cells only during the first seven days after infection. No correlation was found between the severity of the brain lesions and the level of circulating antiviral antibody, preexisting or newly produced.

Animals↗

Persistent parainfluenza type 1 (6/94) infection of brain cells in tissue culture.

A state of persistent infection with parainfluenza type 1 virus (6/94 strain) was established in cultures of human and bovine brain cells. Following primary infection of human brain cells, viral cytopathic effect (CPE) and hemadsorption (HAD) depended on the multiplicity of infection. After persistent infection was established the virus rapidly became cell-associated; no CPE occurred and no viral antigen was detectable by HAD, immunofluorescence (FA), or immunoprecipitation. Infectious virus could be recovered only by fusion or cocultivation. This was in marked contrast with infected bovine brain cells, where, following primary infection, little or no CPE occurred. A productive infection rapidly evolved and persisted without CPE, but with 100 per cent HAD and FA positive cells.

Animals↗

Time sequence and morphological evaluations of cells fused by polyethylene glycol 6000(1).

Mouse L cells (clone 1D) were fused with polyethylene glycol (PEG). The fusion sequence was determined by using sequential light microscopy of the same group of cells, scanning electron microscopy (SEM),transmission electron microscopy, and freeze-etching. The cells were found to fuse only 1 min after PEG had been washed off at small localized areas. Larger fusion images were found after 3 min. Intramembrane particles were observed to have a tendency to aggregate after PEG treatment, but a direct correlation of this activity with the fusion process could not be made. No pathological changes were noted at longer times after PEG removal, except for the extensive widening of the rough-surfaced endoplasmic reticulum (RER) in some cells. It is proposed that fusion does not occur if apposing cells have many microvilli at the area of apparent contact.

Animals↗