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Biomedical subjects

Z Wroblewska

Publications and source records attributed to Z Wroblewska.

53 records · Page 3Linked to original sources

Varicella-zoster virus infection of human brain cells and ganglion cells in tissue culture.

The growth of varicella-zoster virus (VZV) in cultures of human brain (HB) and human ganglion (HG) cells was compared to VZV growth in human fibroblasts. Infected cultures were monitored by histologic, electron microscopic (EM), and virologic techniques. Two to three days after VZV infection of all cell cultures at a multiplicity of infection (MOI) of 0.1, a multifocal cytopathic effect (CPE) developed. CPE was characterized by multinucleated cells and virus-specific intranuclear inclusions as determined by immunofluorescence and EM. In VZV- infected HB and HG cells only, large vacuoles were also seen in the cytoplasm of dying cells. Some vacuoles were almost devoid of structures. Within and at the limiting membranes of other vacuoles, aggregates of VZV particles (measuring 210--230 nm) were seen enveloped in osmiophilic material. VZV infection of HB and HG cultures was strongly cell-associated. Clarified tissue culture medium removed at maximum CPE failed to infect homologous HB or HG cells. When an inoculum of VZV-infected HB or HG cells was transferred to homologous uninfected cultures for 10--15 passages, the incubation period for CPE remained constant, and the titer of VZV in cells sampled randomly corresponded to the amount of virus that was used for original infection.

Brain↗

Virology and histopathology of the trigeminal ganglia of Americans and Japanese.

Herpes simplex virus in the trigeminal ganglia of humans was studied in Philadelphia, Pennsylvania, United States of America, and in Kyoto, Japan. The prevalence of recurrent herpes labialis and of clinically latent herpes simplex virus within trigeminal ganglia was determined in inhabitants of the two cities. In addition, a comparison was made of the prevalence of mononuclear cell infiltration in the trigeminal ganglia of Americans and Japanese. Recurrent herpes labialis was found to be significantly less common in the Japanese city than in the American city. Herpes simplex virus was rescued less commonly from the trigeminal ganglia of cadavers in Japan than in America. The difference was significant. The frequency of mononuclear cell infiltration in the trigeminal ganglia of Americans and Japanese is not significantly different. These observations, as well as previously reported serological studies, suggest that despite the ubiquitous nature of herpes simplex virus in America and Japan, the Japanese have less clinically overt disease caused by this virus.

Adolescent↗

Parainfluenza 1 (6/94) virus-induced white matter degeneration: enhancement by adoptive transfer of virus-sensitized immunocytes.

Intracerebral (i.c.) inoculation of parainfluenza 1 (6/94) virus into weanling Lewis rats produced meningitis, choroiditis, ependymitis, and a rare noninflammatory white matter degeneration (WMD). Adoptive transfer of immune spleen cells (ISC), 3 to 5 days after virus infection, significantly increased the incidence of WMD. Conversely ISC given 2 days prior to virus infection not only protected rats from developing WMD, but also from developing meningitis, choroiditis, or ependymitis. Thus the temporal relationship of 6/94 virus inoculation to the virus-specific immune response appears critical in determining whether WMD will develop in association with 6/94 virus infection. Although sensitized immunocytes may prevent pathologic changes if given prior to virus inoculation, such immunocytes enhance the production of WMD if given after such inoculation. These studies underline the dual role of the immune response in 6/94 virus infection, and indicate that 6/94 virus-induced WMD is, in part, immunemediated.

Animals↗

Herpes simplex virus latency in patients with multiple sclerosis, lymphoma and normal humans.

Herpes simplex virus (HSV) was isolated from the trigeminal ganglia (TG) of 12 cadavers (10 traumatic deaths, one lymphoma and one multiple sclerosis). The cadaver with multiple sclerosis showed large bilateral trigeminal nerve root entry zone areas of demyelination. It is hypothesized that HSV is capable of migrating to the trigeminal nerve root entry zone and initiating demyelinating disease.

Adolescent↗

Isolation of Herpes simplex virus from human trigeminal ganglia, including ganglia from one patient with multiple sclerosis.

Herpes-simplex virus (H.S.V.) was isolated from 18 of 39 trigeminal ganglia (T.G.) obtained within 12 h of death. The virus was isolated from ten persons who had died of trauma, from one case of lymphoma, and from one case of multiple sclerosis. In the cadaver with histologically confirmed multiple sclerosis, large bilateral areas of demyelination were present near the points of entry of the nerve root, and the possibility that H.S.V. migration to the root entry zone caused demyelination cannot be excluded.

Adolescent↗

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↗

Experimental infection of human leukocytes with parainfluenza 1 (6/94) virus.

Parainfluenza 1 (6/94) virus replicated in both unstimulated and phytohemagglutinin (PHA)-stimulated human peripheral blood leukocytes (PBL). After exposure of PBL to 6/94 virus at a multiplicity of infection of 1, the presence of viral antigen was demonstrated by immunofluorescence in the cytoplasm of less than 1% of unstimulated PBL and 1 to 5% of macrophages. Small amounts (less than 50 mean egg infective doses per ml in most instances) of cell-free virus were present in 18 of 30 (60%) cell cultures tested from 3 to 8 days postinfection. Cell-free virus peaked 6 days postinfection. Virus replication was enhanced in PHA-stimulated cells. Approximately 1 to 10% of PHA-stimulated PBL contained viral antigen as evidenced by immunofluorescence, and cell-free virus was present in 19 of 25 (76%) of the cell cultures tested from 3 to 8 days postinfection. Paramyxovirus nucleocapsids and tubular aggregates were seen in the cytoplasm of approximately 5% of PHA-stimulated PBL and were visualized only in lymphocytes. No other unusual intracytoplasmic or intranuclear structures were seen.

Capsid↗

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↗

Human brain in tissue culture. Part. 5. Identification of glial cells by immunofluorescence.

Glial fibrillary acidic (GFA) protein was demonstrated by immunofluorescence in both primary and long-term cultures of adult human brain cells explanted from normal, neoplastic and non-neoplastic CNS diseases, and in mouse brain cells subcultivated in vitro. GFA protein was present in the cytoplasm of at least 4 distinct cell types and persisted throughout the finite lifetime of brain cell cultures.

Brain↗

Experimental panencephalitis induced in suckling mice by parainfluenza type 1 (6/94) virus. I. Clinical and pathological features.

Intracerebral inoculation of two strains of suckling mice with 6/94 virus, a parainfluenza type 1 virus originally isolated from two patients with multiple sclerosis, produced clinical disease 1-2 weeks after inoculation. Of 528 animals inoculated, 33% died (26% of the ICR strain and 76% of the BALB/c strain) usually between two or three weeks after injection. Animals that recovered appeared to develop normally. Pathological changes were of two types. Initially, there was a necrotizing panencephalitis with virus-specific intracytoplasmic inclusions in choroid and ependymal epithelial cells and neurons. The second major lesion appeared about 6 weeks post inoculation and consisted of a noninflammatory spongiform degeneration of white matter that primarily involved the cerebral hemispheres; a diffuse vacuolar encephalapathy primarily affecting the brain stem; and a persistent minimal inflammation.

Animals↗

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↗

Human brain in tissue culture. I. Acquisition, initial processing, and establishment of brain cell cultures.

This paper details the in vitro techniques used to establish cells in culture from the brains of 40 patients, most of whom had chronic neurologic disease. The clinical and pathologic features of these patients are given. The success in establihsing cell lines was dependent upon the origin of tissue (biopsy vs. autopsy), the site of removal from the brain, and various environmental and technical manipulations in vitro.

Adolescent↗

Human brain in tissue culture. II. Studies of long-term cultures.

This paper describes the techniques used to maintain and reconstitute from storage adult human brain cells in culture. Growth characteristics, cell morphology, lifespan, and karyotypic analysis of cell lines derived from patients with multiple sclerosis (MS), non-MS neurologic diseases, and normal brains are compared.

Aging↗

Human brain in tissue culture. III. PML-SV40-induced transformation of brain cells and establishment of permanent lines.

Cells from explants and monolayer subcultures of adult human brain obtained from biopsies or autopsies of ten multiple sclerosis (MS) cases, one case each of Jakob-Creutzfeld (JC) and amyotrophic lateral sclerosis (ALS) and three cases with no central nervous system (CNS) involvement were transformed with PML-SV40 virus. Transformation was effected to establish permanent lines of these particular adult brain cells so that sufficient quantities would be available for other research projects. The procedure previously used to transform human fibroblasts (Koprowski et al., '62) was successfully applied to human brain cells. The success of transformation was dependent on the growth condition of the cultures at the time of infection. Events occurring after viral infection and during the pre-transformation and the post-transformation phases are described.

Amyotrophic Lateral Sclerosis↗

Human brain in tissue culture. IV. Morphological characteristics.

The morphology of cells from normal and diseased brains and PML-SV40 transformed brain cells grown on glass cover slips in cultures is described. Seven types of cells are identifiable, four of which are probably of mesenchymal origin whereas the remaining three are neurologlial. A classification on the basis of the morphologic features is presented.

Amyotrophic Lateral Sclerosis↗

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↗