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Biomedical subjects

H Koprowski

Publications and source records attributed to H Koprowski.

At least 433 records · Page 24Linked to original sources
PubMed1975

Paramyxovirus-like structures in brains of multiple sclerosis patients.

Twenty-four plaques obtained at autopsy from the brains of six patients with multiple sclerosis were examined under an electron microscope. Specimens for ultrastructural study were processed from the unfixed brain tissues at the time of autopsies. Intranuclear filaments with a diameter of 150 to 260 Angstroms of possibly two different types were seen in the macrophages and in unidentified mononuclear cells that were infiltrating the perivascular regions of four plaque areas from three patients. Intracytoplasmic reticular filaments with a diameter of 100 to 130 A were seen in the astrocytes and in unidentified cell processes in five plaques from three cases. A possible link between these intranuclear filaments and paramyxovirus is suggested.

Astrocytes↗
PubMed1975

Hydrocephalus produced by the 6/94 virus; A parainfluenza type 1 isolate from multiple sclerosis brain tissue.

The 6/94 virus, parainfluenza type 1 isolate from multiple sclerosis brain tissue, produced hydrocephalus in newborn Syrian hamsters. All animals developed clinical disease and died within a week. Ependymal cells lining the aqueduct of Sylvius became necrotic and fused, resulting in obstructive hydrocephalus. The 6/94 virus antigen was seen in ependyma and meninges. Paramyxovirus nucleocapsids were seen within cytoplasm of ependymal cells. Virus was recovered from hamster brains for only two days. Infectious virus could be recovered from brains grown in vitro as explants for 21 days. No evidence of rising hemagglutination-inhibiting antibody was noted for up to one month after infection. Intraperitoneal or subcutaneous injection of 6/94 virus did not produce hydrocephalus. HA2 virus and the temperature sensitive mutant of HA2 virus failed to produce hydrocephalus, while Sendai virus caused lesions similar to those of 6/94 virus.

Animals↗
PubMed1975

Mouse embryo development in vitro: effects of inhibitors of RNA and protein synthesis on blastocyst and post-blastocyst embryos.

The effect of inhibitors of RNA synthesis (Cordycepin, Actinomycin D) and protein synthesis (Cycloheximide) on the development and growth of mouse blastocysts in vitro was explored. Blastocysts exposed in vitro for 24 hours to 50 mu-g/ml Cordycepin, 0.005 mu-g/ml Actinomycin D, or 0.1 mu-g/ml Cycloheximde grew and began to attach to the dish in the similar manner as did the controls. Cell number, 3-H-thymidine-labeling index and mitotic index in treated blastocysts were also similar to controls. Cell number, 3-H-thymidine-labeling index and mitotic index in treated blastocysts were also similar to controls. Control blastocysts grown in vitro for six days attached to the dish, trophoblastic layer was spread and inner cell mass continued to grow and formed an egg-cylinder like structure. Blastocysts grown in constant presence of 50 mu-g/ml of Cordycepin in themedium or those exposed to inhibitor only for the first 24 hours failed to develop inner cell mass derivatives in culture, although the growth of trophoblastic cells was as in controls. The same results were obtained if blastocysts were exposed to 0.005 mu-g/ml of Actinomycin D or to 0.1 mu-g/ml of Cycloheximide either continuously or for the first 24 hours. Higher concentrations of Actinomycin D (0.05 mu-g/ml) or Cycloheximde (1 mu-g/ml) were toxic for the blastocysts causing their degeneration within 24-48 hours. Our results suggested that appropriate concentrations of RNA or protein synthesis inhibitors could prevent the development of inner cell mass derivatives with essentially no effect on the development of primary trophoblast. This would indicate that the process of differentiation of inner cell mass cells is much more sensitive to metabolic inhibitors than the differentiation of giant trophoblastic cells.

Animals↗
PubMed1975

Early sterile autopsy in etiological studies on multiple sclerosis.

The clinical findings and course in the first 2 cases of multiple sclerosis are described, in whom it was possible to isolate a virus from brain tissue by early sterile autopsy and fusion technique. It is noteworthy that in one of these cases multiple sclerosis probably occurred in female members of the family through three consecutive generations. A report is made on an additional case, in which no virus could be isolated, but in which electron microscopic studies showed two types of virus particles: nucleocapsid-like structures and particles identical in form and size with papova virus. Electron microscopic findings and attempts to cultivate a virus in multiple sclerosis published by other authors are discussed. It is pointed out, that the results described provide as yet no proof for the viral etiology of multiple sclerosis. They support the hypothesis, however, that a virus may play an essential role in the etiology and/or pathogenesis of this disease. Problems in relation to brain autopsy in multiple sclerosis are discussed. Early sterile autopsy is considered the most practicable possibility for obtaining tissue material for culturing and for ultrastructural studies in multiple sclerosis.

Adult↗
PubMed1975

Multiple sclerosis and parainfluenza 1 virus. History of the isolation of the virus and expression of phenotypic differences between the isolated virus and Sendai virus.

54 cultures were established from brain tissue obtained 2-3 hrs after death from 1 case of multiple sclerosis and 30 cultures from another case. Following fusion with indicator cells in the presence of lysolecithin, a parainfluenza type 1 virus (6/94 virus) was isolated from cultures representing one plaque area in the first case and one plaque area in the second case. A cell line chronically infected with the 6/94 virus has been maintained for more than 100 passages in vitro. A close relationship to the Sendai Hemagglutinating Virus of Japan (HVJ) is indicated from RNA-RNA hybridization and the patterns of electrophoretic mobilities of viral polypeptides. Conversely, differences in optima for growth-requirement temperatures, hemolytic activity and the capability to fuse mammalian cells, distinguishes 6/94 virus and HVJ as distinct phenotypic entities of a closely related genotype.

Adult↗
PubMed1975

Sporadic bovine meningo-encephalitis-isolation of a paramyxovirus.

Isolation of a viral agent (107) directly from brain explants of a 15-month-old heifer with symptoms of a sporadic encephalomyelitis is described. The virus shares properties with the paramyxovirus family. It grows in a variety of cell cultures from different species, and induces nuclear and cytoplasmic inclusion bodies in infected cells. Nucleocapsids measuring 17 nm in diameter were found in the nucleus and cytoplasm of these cells when studied electron microscopically, thus indicating a close relationship of the agent to the measles-distemper-rinderpest group. No infectious virus was released from infected cells, although alignment of nucleocapsids was observed beneath the cell membrane, and no hemagglutinating activity could be detected with the methods employed. The 107 agent was compared serologically with parainfluenza viruses type 1, 2 and 3, simian virus 5, mumps and Newcastle disease virus (NDV), two bovine respiratory syncytial viruses and measles/subacute sclerosing panencephalitis, distemper and rinderpest viruses, always using 107 virus infected CV1 cells and antiserum of the different viruses in indirect FA tests. Positive FA reactions were observed only with two sera obtained from SSPE patients with high antibody titer to SSPE virus, and with one rabbit-anti-rinderpest serum. The titers of these sera to 107 virus, however, were significantly lower than those against homologous viruses. Five out of 9 sera from randomly selected healthy cattle showed antibody titers between 1:10 and 1:80 to 107 virus in FA tests. The significance of these results is discussed with respect to the epidemiology of SSPE in children and its possible implication with rinderpest in Europe.

Animals↗
PubMed1975

Establishment of continuous multiple sclerosis brain cultures after transformation with PML-SV40 virus.

PML-SV40 virus was used to transform cells from explants and monolayer subcultures of human brain derived from biopsies or autopsies of MS cases, as well as from 1 case of Jakob-Creutzfeldt disease (JC), 1 case of amyotrophic lateral sclerosis (ALS) and several cases without CNS disease. The success of transformation depended on the growth condition of the culture at the time of infection but at present at least 14 cell lines, 10 derived from MS, 2 from JC, 1 from ALS and 1 from a normal non-CNS patient are maintained in continuous culture.

Amyotrophic Lateral Sclerosis↗
PubMed1975

Structure-function relationships and mode of replication of animal rhabdoviruses.

Recently accumulated knowledge allows more precise comparison of the structural (and possibly evolutionary) relationships of several different animal rhabdoviruses: vesicular stomatitis virus, rabies virus, Kern Canyon virus, and spring viremia of carp virus. Each virus is composed primarily of a glycoprotein, an RNA-associated nucleoprotein, and one or two membrane proteins. Vesicular stomatitis virus group viruses contain lesser amounts of two additional distinct polypeptides, NS and L. The separate viruses undergo structural polypeptide phosphorylation in vivo according to characteristic patterns. In vesicular stomatitis virus the NS protein is selectively phosphorylated. In rabies group viruses and in spring viremia of carp virus, the nucleoprotein is the predominant phosphoprotein; in these viruses only the phosphorylated moiety is selectively cleaved off with trypsin. In Kern Canyon virus, only membrane protein and glycoprotein are weakly phosphorylated. Each virus possesses a virion-bound protein kinase. Vesicular stomatitis virus group viruses, Kern Canyon virus, and spring viremia of carp virus only contain virion-bound transcriptases of respectively decreasing levels of activity demonstrable in vitro. Vesicular stomatitis and Kern Canyon viruses replicate efficiently in enucleated cells; rabies virus does not. Based upon these observations, it is suggested that vesicular stomatitis virus may represent the most highly evolved of these rhabdoviruses, whereas spring viremia of carp and Kern Canyon viruses may represent "evolutionary links" between the vesicular stomatitis and rabies virus groups.

Animals↗
PubMed1975

Somatic cell hybrids between mouse peritoneal macrophages and simian-virus-40-transformed human cells: II. Presence of human chromosome 7 carrying simin virus 40 genome in cells of tumors induced by hybrid cells.

Cells derived from tumors induced in "nude" mice after injection of cells that were hybrids between mouse peritoneal macrophages and simian virus 40 (SV40)-transformed human cells were found to retain the human chromosome 7 carrying the SV40 genome, and indicate that the presence of human chromosome 7 carrying the SV40 genome is responsible for the expression of the tumorigenic phenotype in the hybrid cells.

Animals↗
PubMed1975

Assignment of gene(s) for cell transformation to human chromosome 7 carrying the simian virus 40 genome.

Somatic cell hybrid clones between either C57BL/6 or Balb/c mouse peritoneal macrophages and two different simian virus 40 (SV40)-transformed human cell lines deficient in hypoxanthine phosphoribosyltransferase (EC 2.4.2.8; IMP:pyrophosphate phosphoribosyltransferase) were obtained in hypoxanthine-aminopterin-thymidine selective medium. All the hybrid cell clones contained the human chromosome 7, which carries the SV40 genome, and were SV40 tumor (T)-antigen positive. No hybrid cell clones studied displayed the density-dependent inhibition of cell growth characteristic of normal cells; all clones had a high saturation density and gave origin to cell colonies when plated in soft agar. Since the expression of the transformed phenotype was always associated with the presence of the human chromosome 7, which carries the SV40 genome, it is concluded that this chromosome contains gene(s) [Tr gene(s)] coding for "transforming factor(s)."

Animals↗
PubMed1975

Genetics of cell transformation by simian virus 40.

The results described in this paper indicate that the integration of the SV40 genome into human chromosome 7 results in the transformation of the human cells and in the expression of SV40-induced antigens. If integration of the SV40 genome in human chromosomes other than 7 ever occurs, it does not result in cell transformation and the expression of the virus-induced antigens. The expression of the SV40 T antigen in different monkey cells transformed by an adeno 7-SV40 hybrid is also related to a specific monkey chromosome. Somatic cell hybrids between normal nondividing mouse cells and SV40-transformed human cells behave as transformed cells and contain, without exception, the human chromosome 7 carrying the SV40 genome. Since no segregation into SV40 T antigen-negative hybrid clones was observed in these hybrids, it is inferred that the presence of the human chromosome 7 carrying the SV40 genome in the hybrids is mandatory for cell division.

Antigens, Neoplasm↗
PubMed1975

Antigenic variation among parainfluenza type 1 (Sendai) viruses: analysis of 6/94 virus.

6/94 virus, isolated originally from a multiple sclerosis (MS) patient, was compared antigenically with related parainfluenza type 1 strains. These included two Sendai strains of mouse and two Sendai strains of reported human origin as well as the HA2 strain. By standard hemagglutination inhibition (HI) or hemadsorption neutralization (HAD-N) tests or by the complement-fixation (CF) cross-block titration test for detecting surface antigens, 6/94 virus and the Sendai virus strains were indistinguishable from each other but distinct from the HA2 strain. By the kinetic HI test, however, 6/94 virus could be readily differentiated from the Sendai viruses isolated from mice and more closely resembled those recovered from man.

Animals↗
PubMed1975

In vitro cellular responsiveness in multiple sclerosis patients to a viral isolate from multiple sclerosis brain tissue and to other antigens.

The Clausen modification of the leukocyte migration test was used to test patients with multiple sclerosis, normal subjects, and patients with other neurologic diseases for cell-mediated immunity to 6/94 virus (a parainfluenza virus previously isolated from the brain tissue of a multiple sclerosis patient), c-RNA virus isolated from a tumor, and the nonviral antigens Candida and purified protein derivative. Leukocytes of multiple sclerosis patient showed significantly less mean inhibition of migration by the 6/94 virus (but not by the c-RNA virus, purified protein derivative, and Candida) than did the cells of normal controls and patients with other neurologic diseases. The relationship of these findings to previous observations in this area and to the pathogenesis of multiple sclerosis is discussed.

Antigens, Viral↗
PubMed1975

Reversion in expression of hypoxanthine-guanine phosphoribosyl transferase following cell hybridization.

Hybridization of mutant cell lines deficient in hypoxanthine-guanine phosphoribosyl transferase (HGPRT; E.C.: 2.4.2.8) from a variety of established rodent sources with HGPRT plus human cells yielded progeny cells which grew in selective medium containing hypoxanthine, aminopterin and thymidine (HAT). The same result was obtained when the human cell used was an HGPRT minus transformed line derived from a patient with the Lesch-Nyhan syndrome. Electrophoretic analysis indicated that all HAT-resistant progeny clones contained an active HGPRT enzyme which was indistinguishable from the wild type enzyme of the corresponding normal rodent cells. In contrast, no HAT-resistant cells have been obtained when the same HGPRT minus rodent cells were subjected to fusion processes in the absence of human cells or when they fused with similarly derived HGPRT minus mutant cells of other rodents. Reversion in expression of the rodent gene for HGPRT was detected in clones which retained one or more human chromosomes and in clones which contained no detectable human chromosomal material. The observed re-expression of rodent HGPRT in HAT-resistant clones suggests that HGPRT plus as well as HGPRT minus human cells contributed a factor which determined the expression of respective rodent structural genes for HGPRT. In contrast, HGPRT minus rodent cells were unable to induce the synthesis or normal HGPRT in the cells derived from the patient with the Lesch-Nyhan syndrome.

Aminopterin↗
PubMed1975

Lipids and cell fusion in vitro: effect of amphotericin B.

Fusion rate of Cl-1D cells mediated by Sendai virus was decreased by preincubating the cells or the virus in the presence of lysolecithin. However, a significant increase occurred when the cells were preincubated in the presence of amphotericin B. This increase was suppressed by exogenous cholesterol.

Amphotericin B↗
PubMed1975

Pathogenesis of rabies in immunodeficient mice.

The HEP and ts2 strains of rabies virus inoculated intracerebrally into adult mice normally cause clinically inapparent infection. In the experiments described, this is converted into a lethal infection by immunosuppression with cyclophosphamide, which also prevented induction of immunity with vaccine. Lethal infection of HEP-inoculated mice was also observed in mice treated with antihymocytic serum, and in athymic (BALB/c-nu) nude mice.

Animals↗