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Biomedical subjects

F S Lief

Publications and source records attributed to F S Lief.

At least 19 recordsLinked to original sources
PubMed1979

I-cell disease: intracellular desialylation of lysosomal enzymes using an influenza virus vector.

It has been proposed that I-cell disease results from a primary deficiency of acid neuraminidase activity. Infection by influenza virus of fibroblasts from a patient with I-cell disease resulted in the production of abundant intracellular alpha2-3 neuraminidase activity. Despite electrophoretic evidence of desialylation of intracellular and fibroblast-secreted arylsulfatase (EC 3.1.6.1) and beta-hexosaminidase (EC 3.2.1.30) from the infected cells, there was no consequent alteration of the abnormal distribution of beta-hexosaminidase activity between the intracellular spaces characteristic of I-cell disease. This suggests that deficiency of alpha2,3 neuraminidase activity is not the primary biochemical defect in I-cell disease.

Arylsulfatases↗
PubMed1979

Acute demyelinating disease in a chimpanzee three years after inoculation of brain cells from a patient with MS.

Brain cells from a patient with classic multiple sclerosis were inoculated intracerebrally into the frontal lobe of a newborn chimpanzee. The animal developed acute quadriplegia three years, two months later and was killed four days after the onset of symptoms. Central nervous system lesions were primarily localized in the spinal cord at root entry zones; these were characterized by demyelination and regeneration of myelin by Schwann cells.

Animals↗
PubMed1979

Fer de Lance virus (FDLV): a probable paramyxovirus isolated from a reptile.

A new virus has been isolated by inoculation of lung tissues of diseased snakes into snake embryos. Homogenates of infected embryo tissues caused c.p.e. in cell cultures incubated at 30 degrees C. The virus replicates in a wide variety of reptilian or mammalian cell types incubated at 30 degrees C, inducing either syncytium formation or minimal or no cytopathic changes. Efficient replication occurs in embryonated hens' eggs at 27 to 30 degrees C. The virus haemagglutinates guinea pig and chick erythrocytes; it possesses a neuraminidase similar to the receptor-destroying enzyme of Vibrio cholera. Electron microscopic observations of infected cells examined in thin section revealed pleomorphic viruses 146 to 321 nm in diam. resembling known myxoviruses. Internal nucleocapsid strands are 15 to 16 nm in diam.; nucleocapsid observed in negatively stained preparations measures 14 nm in diam. The virus was determined to possess a nucleoprotein core containing a 50S single-stranded unsegmented RNA genome. All characters of the virus are similar to those of the paramyxovirus group except that the nucleocapsid diam. is intermediate between that of paramyxoviruses and pneumoviruses. The virus is antigenically distinct from known myxoviruses and is unique among myxoviruses in its restriction to growth at temperature below 37 degrees C.

Animals↗
PubMed1979

Interaction between 6/94 virus, a parainfluenza type 1 strain, and mouse macrophages.

The 6/94 virus, a type 1 parainfluenza virus recovered from multiple sclerosis brain cells after lysolecithin-induced fusion of these cells with African green monkey kidney cells (CV-1), has been found to grow in splenic and peritoneal macrophages obtained from outbred and different strains of inbred mice. Macrophages from C57BL animals were least susceptible to infection, a resistance apparently partially age related. The virus also has been found to replicate in IC21 cells, a line of simian virus 40 virus-transformed mouse macrophages. Viral growth was detected by development of hemadsorption in infected cells, followed by the appearance of infectious virus. The growth of 6/94 virus had different kinetics in mouse macrophages, in the standard continuous cell lines L, 3T3, and CV-1, and in primary mouse kidney and mouse embryo cells. The virus produced in macrophages could be passed in series to other macrophage cultures. In addition, once infected, the cultures continued to produce virus, and permanently infected cell lines were thus obtained. Macrophages from immunized mice with high titers of humoral neutralizing antibodies were found variably able to support virus growth.

Animals↗
PubMed1979

Interaction between 6/94 virus, a parainfluenza type 1 strain, and unstimulated mouse lymphocytes.

6/94 virus was found to grow in unstimulated splenic mouse lymphocytes depleted of monocyte macrophages. Both egg-grown virus and virus produced in mouse macrophage cultures induced the development of hemadsorption and the appearance of new infectious virus in the lymphocyte cultures. An antigenic relative. Sendai virus, on the contrary, was quickly inactivated in these lymphocyte cultures, in agreement with previous reports in the literature. The T lymphocyte population seemed to be the fraction principally involved in the replication of 6/94 virus. The immunization of mice with 6/94 virus and the appearance of high levels of humoral neutralizing antibodies did not inhibit completely the susceptibility of their lymphocytes to the infectious agent.

Animals↗
PubMed1979

Interaction between 6/94 virus, a parainfluenza type 1 strain, and human leukocytes.

6/94 virus, a parainfluenza type 1 virus recovered by lysolecithin fusion of multiple sclerosis brain cell cultures with CV-1 cells, replicated in monocyte macrophages and lymphocytes from normal human donors and from a patient with multiple sclerosis. In macrophage cultures, hemadsorption-positive cells and high levels of infectious virus became apparent within 24 to 48 h after infection, persisted for 6 days, and then began to decrease. Phytohemagglutinin-stimulated macrophages yielded similar titers of virus, but the levels were maintained for a longer period of time. Macrophage-produced virus appeared to be infectious for other macrophages in the same culture. Both unstimulated and phytohemagglutinin-stimulated lymphocytes also supported virus replication. Significantly higher titers were produced in the stimulated cultures, T cell-enriched populations producing more virus than unseparated populations whether stimulated or unstimulated. The presence or absence of antibodies to the virus in the donors did not appear to influence the levels of virus obtained in any of the leukocyte cultures. However, an increase in blastic forms after 6/94 virus infection was noted in lymphocytes from donors with antibodies as revealed morphologically and by increased incorporations of tritiated thymidine. Furthermore, 6/94 virus-infected lymphocytes, unlike Sendai virus-infected lymphocytes, were able to respond well to mitogenic stimulation by phytohemagglutinin.

Antibodies, Viral↗
PubMed1979

Rapid diagnosis of influenza A infection by direct immunofluorescence of nasopharyngeal aspirates in adults.

The efficacy for direct immunofluorescence of a commercial conjugate for influenza A virus prepared against whole A/Udorn (H3NS) virus was studied. The conjugate was specific for influenza A virus, but its sensitivity varied depending upon the strain of influenza A tested. Nasopharyngeal aspirates collected from 25 patients during an outbreak of influenza were examined for viral antigen with the conjugates and inoculated onto monkey kidney (MK) cells for virus isolation. Fifteen patients had isolates for influenza A/USSR/90/77 (H1N1); nasopharyngeal secretions were fluorescent antibody positive in 12. Fluorescent antibody was copositive with culture in 11/15 patients (73.3%) and conegative in 9/10 (90%). The one fluorescent antibody-positive, culture-negative patient had negative serology for influenza A and the fluorescent antibody result was considered to be a false positive. At a 1:10 dilution, the conjugate stained nasopharyngeal and MK cells infected with A/USSR (H1N1) 2 to 3+, whereas cells infected with H3N2 virus stained 4+. A conjugate made specifically against the ribonucleoprotein antigen, which is universal to all influenza A strains, may improve the sensitivity of the direct immunofluorescent test.

Adult↗
PubMed1978

Cell-mediated cytotoxicity against virus-infected target cells in humans. I. Characterization of the effector lymphocyte.

In a 51Chromium release assay performed without immune sera, purified lymphocytes from randomly selected healthy donors killed significantly more allogeneic virus-infected than noninfected fibroblasts. An incubation period of 18 to 20 hr was optimal for determining cytotoxicity, but increased cytotoxic activity against infected cells was observed as early as 6 hr from the start of the test. No correlation could be found between donors' antibody titers to any virus tested and the cytotoxic efficiency of their effector cells: virus-infected cells were lysed by both seropositive and seronegative individuals. With several different cell fractionation techniques, the effector cell in this system could not be distinguished from the human natural killer cell, which is a lymphocyte with receptors for the Fc fragment of IgG but with no surface immunoglobulin. When lymphocytes were separated on the basis of ability to form rosettes with neuraminidase or AET (2-aminoethylisothiouronium bromide hydrobromide)-treated sheep erythrocytes, the majority of cytotoxic activity was consistently recovered in the nonrosetting fraction. A portion of it, however, was always present in the rosetting fraction and was, again, mediated by lymphocytes carrying receptors for the Fc fragment of IgG.

Adult↗
PubMed1977

Acute optic neuritis: a virological study in relation to multiple sclerosis.

Previous ultrastructural examination of peripheral blood lymphocytes revealed the presence of intranuclear filamentous structures in multiple sclerosis (MS) and in some optic neuritis (ON) patients. The present investigation was undertaken in the attempt to correlate the presence of such structures with the etiology of ON and MS and possibly to demonstrate the viral origin of the filaments. Suitable virological and serological techniques were used to detect and isolate infectious agents from peripheral blood samples and body excretions of 12 monosymptomatic ON patients at their first acute attack. Nevertheless, any efforts to demonstrate the presence of a virus in these patients have been unsuccessful: no evidence of active viral infection was obtained by serological studies of serum and cerebrospinal fluid samples, nor could viral antigens or inclusions be observed by immunofluorescence and cytochemical analysis. Negative results were also obtained from studies performed in parallel on MS patients and various controls. The significance of the failure to isolate infectious agents from either ON and MS patients is discussed.

Acute Disease↗
PubMed1976

Experimental panencephalitis induced in suckling mice, by parainfluenza type 1 (6/94) virus, II. Virologic studies.

6/94 virus, a parainfluenza type 1 isolate from multiple sclerosis brain tissue, produced a chronic panencephalitis when inoculated intracerebrally into suckling ICR mice. Immunofluorescent staining revealed 6/94 viral antigen in ependyma, meninges, choroid plexus, and perivascular parenchymal sites from day 3 to 128 days after infection. Hemadsorption-neutralizing antibody was first detected between 20-25 days after infection and remained at high titers for 7 months. Using embryonated chicken eggs, virus was recovered from mouse brains for only 8 days, but could be recovered from brains grown in vitro as explants for 37 days after infection. In cell lines established from explanted brain tissue, immunofluorescence was the most sensitive indicator of virus presence, although infectious virus was not produced. Fusion of these mouse brain cells with human (W138) indicator cells was the most effective means of rescuing 6/94 virus.

Animals↗
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

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↗
PubMed1974

Specific and nonspecific cell-mediated resistance to influenza virus in mice.

We found that influenza virus had the capacity to replicate in the peritoneal macrophages of normal mice, as revealed by the development of hemadsorption and the appearance intracellularly of S and V antigens. Cell-mediated resistance was studied in mice infected with influenza virus or a bacterial sytem of induction-elicitation. In the homologous system, mice were injected intraperitoneally or exposed by aerosol to a sublethal dose of an egg-adapted swine strain of influenza virus. In the heterologous system, they were infected repeatedly with Staphylococcus aureus and elicited by subcutaneous or aerosol administration of staphylococcal antigens. The peritoneal macrophages from mice specifically or nonspecifically immunized were significantly more resistant than those from normal mice. Also longer survival to in vivo challenge by the mouse-adapted virus, as compared with normal mice, was indicated in bacterially stimulated mice.

Aerosols↗
PubMed1974

Analysis of a viral agent isolated from multiple sclerosis brain tissue: characterization as a parainfluenzavirus type 1.

A virus originally isolated from cell cultures obtained by lysolecithin-induced fusion of human multiple sclerosis brain cells with CV-1 cells has been analyzed for its antigenic, RNA, and polypeptide compositions, and for selective biological properties. Our findings establish that this isolate, designated 6/94 virus, contains a 50S RNA genome and is, as yet, indistinguishable from Sendai virus in its antigenic and total polypeptide compositions. Despite these similarities, the 6/94 and Sendai viruses differ in certain phenotypic properties. 6/94 virus is markedly less cytocidal for chick fibroblasts, especially at 37 C and, after beta-propiolactone inactivation, it possesses a greater capacity for cell fusion and a lower toxicity than does comparably treated Sendai virus. In addition, 6/94 virus shows greater hemolytic activity.

Animals↗
PubMed1972

Epidemiological studies of A-Hong Kong-68 virus infection in dogs.

Experimental inoculation of dogs with the A/Hong Kong/68 influenzavirus resulted in subclinical infection. The virus was readily passed to contacts in the same cage when the latter were exposed in the same inoculation room 24 hours after experimental infection. Removing the site of contact to a noncontaminated room or delaying contact until 48 hours after experimental inoculation greatly reduced the possibility of infection in contact animals. A survey of 271 canine serum samples obtained after a human epidemic from different geographical areas of the USA and the United Kingdom showed that 5.9% of the samples were positive; no positive reactions were found among 111 pre-epidemic samples. These studies demonstrated the laboratory and natural susceptibility of dogs to the Hong Kong variant and suggest the possible role of dogs in the epidemiology of human influenza.

Animals↗