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Biomedical subjects

J S Wolinsky

Publications and source records attributed to J S Wolinsky.

At least 127 records · Page 7Linked to original sources
PubMed1981

Comparison of human cytomegalovirus growth in MRC-5 human fibroblasts, brain, and choroid plexus cells in vitro.

Cell cultures derived from human brain, choroid plexus, and human lung fibroblasts (MRC-5) were infected with the Towne strain of human cytomegalovirus (CMV). The cytopathic effect, beginning 24-48 hours after infection, was characterized by foci of enlarged rounded cells that spread slowly and eventually coalesced to destroy the entire monolayer within one week. Cowdry type A inclusion bodies and herpes virus nucleocapsids were seen in infected cells. CMV-specific antigen was demonstrated by immunofluorescence in fibroblasts and astrocytic cells of brain cultures and in cells of choroid plexus cultures as well as in MRC-5 fibroblasts. Despite these morphologic and immunochemical similarities the growth of CMV differed in cells of brain and choroid plexus origin as compared with MRC-5 cells. In brain and choroid plexus cell cultures most of the virus remained cell-associated throughout the observation period of one week, whereas in MRC-5 cells the CMV was found in both cell-associated and cell-free fractions of harvested material.

Antigens, Viral↗
PubMed1981

Primary culture of capillary endothelium from rat brain.

To provide an in vitro system for studies of brain capillary function we developed a method for culture of brain capillary endothelial cells. Capillaries were isolated from rat brain and enzymatically treated to remove the basement membrane and contaminating pericytes. Subsequent Percoll gradient centrifugation resulted in a homogeneous population of capillary endothelial cells that attached to a collagen substrate and incorporated [3H]thymidine. Evidence for the endothelial nature of these cells was provided by the presence of Factor VIII antigen and angiotensin converting enzyme activity and by the failure of platelets to adhere to the cell surface. In addition, the cells were joined together by tight junctions. Thus, primary cultures of these cells retained both endothelial and blood-brain barrier features.

Animals↗
PubMed1981

Neutralizing antibody spectrum determines the antigenic profiles of emerging mutants of visna virus.

The visna viruses are antigenically related nononcogenic retroviruses of sheep. The original strain was isolated from the brain of a paralyzed sheep in Iceland during the 1940s. The prototype strains has been passed serially in sheep and has undergone progressive antigenic change. Previous reports have shown that such antigenic changes in visna virus can be reproduced in infected cell cultures treated with neutralizing antibody. We now show that the antigenic profiles of the emerging mutants directly reflect the nature of the selecting antibody. Mutants with minor antigenic changes were selected by "early" sera which had a limited neutralization range. Mutants with greater antigenic changes were selected by "late" sera with a wide neutralization range. Mutants selected by early sera emerged rapidly and consistently in cultures, and these were antigenically very similar to one another. Mutants rarely emerged in cultures treated with late sera, but these viruses showed major antigenic changes. The data suggest that the evolution of antigenic mutants of visna virus progresses by a series of minor mutations which accumulate under the selective pressure of antibody.

Animals↗
PubMed1980

Cerebrospinal-fluid lymphocyte populations and immune complexes in active multiple sclerosis.

A specific subpopulation of mononuclear cells bearing a surface receptor for the Fc portion of IgG was considerably reduced in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients during exacerbation, but returned toward normal levels as the patient entered remission. Low concentrations of immune complexes were found in the CSF in nearly 50% of MS patients during exacerbations but immune complexes were not found in patients with stable MS.

Acute Disease↗
PubMed1980

Electron probe microanalysis of isolated brain capillaries poisoned with lead.

The blood-brain barrier has been proposed as an important site for the toxic action of lead in the central nervous system. To investigate this, capillary endothelial cells were isolated from rat cortex and exposed to lead in vitro. Tissue suspensions were then prepared for electron microscopy and X-ray microprobe analysis. In cells exposed in vitro to lead, electron-dense deposits were observed within mitochondria. With X-ray analysis, it was determined that these intramitochondrial deposits contained lead in a non-crystalline matrix. Also, lead appeared to be accumulated in the same intramitochondrial areas as calcium. The results suggest that lead is preferentially sequestered in mitochondria of capillary endothelial cells. Further, this selective localization may be associated with lead-induced disruptions in intracellular calcium metabolism and transepithelial transport processes.

Animals↗
PubMed1980

Measles retinopathy. A hamster model of acute and chronic lesions.

Measles and subacute sclerosing panencephalitis strains of virus inoculated intracerebrally in suckling and weanling hamsters spread immediately to the eye via the blood. Virus replicates in the brain and eye in parallel, and in higher titers than it does in other organs. Acute retinal lesions consist of focal syncytia, inclusion-bearing cells, and necrosis. Immunofluorescence studies show measles-specific antigen in the affected cells. Ultrastructurally, measles nucleocapsids and virions are seen in the retinal cells. The necrosis is followed by a differential repair of the retinal layers that results in retinal dysplasia. Chronically, the retinal dysplasia progresses to atrophy and gliosis of the retina. The chronic lesions are histologically similar to those seen in human subacute sclerosing panencephalitis and measles retinopathies.

Animals↗
PubMed1979

Neuronal and oligodendroglial infection by the WW strain of Theiler's virus.

Newborn ICR mice were infected by intracerebral inoculation of 10(5.3) LD50 of the WW strain of Theiler's virus and examined serially by virologic and ultrastructural methods. Maximal titers of 10(6) LD50 developed in the brain by day 8 when 90 per cent of the animals were dead or moribund. The virus first appeared and was most prominent in the thalamus, basal ganglia, and midbrain. It spread from these areas throughout the cortex, brainstem, and spinal cord but spared the cerebellar cortex. Both neurons and oligodendroglia were infected. Infected cells first showed dispersion of polyribosomes, accumulation of vesicles, and widening of perinuclear cisternae. Normal cytoplasmic organelles and the nucleus were displaced by an accumulation of viral crystals, membranous profiles, and fibrillar material. Within degenerating cells the nuclear chromatin became clumped and marginated and the cytoplasm was filled either with vesicles or masses of paracrystalline viral arrays. These changes were accompanied by a vigorous inflammatory response of lymphocytes, plasma cells, macrophages, neutrophils, and eosinophils. Lysis of oligodendroglia during acute infection with the WW strain of Theiler's virus may provide a stimulus for the late autoimmune demyelination that has been described in animals that survive the acute encephalitis.

Animals↗
PubMed1979

Progressive rubella panencephalitis: immunovirological studies and results of isoprinosine therapy.

Two patients with progressive rubella panencephalitis, one with and one without stigmata of congenital rubella, were treated for 9 months with isoprinosine and showed continued clinical deterioration. Immunoviorological studies performed before, during and after treatment were unaffected by drug therapy. The virus was recovered on one occasion from the lymphocytes of one of these cases. Neither patient showed any major defects in cellular or humoral immunity. However, the lymphocytes of the patient with stigmata of congenital rubella failed to respond to rubella virus in vitro and had a heat stable, non-dialysable serum inhibitor of in vitro protein A stimulated proliferative responses. Both patients' serum interfered with the production of interferon by normal donor lymphocytes following stimulation with rubella and varicella virus antigen. Increasing serum titres of interferon which did not appear to be lymphoid or immune-specific in origin were found in these two cases.

Adolescent↗
PubMed1978

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↗
PubMed1978

Virulence and persistence of three prototype strains of mumps virus in newborn hamsters.

Neuroadapted mumps virus (NMV) produces widespread central nervous system (CNS) disease and death after intracerebral (i.c.) inoculation of newborn hamsters. After intraperitoneal (i.p.) inoculation, NMV causes disseminated disease, moderate mortality and it persists in CNS tissues. Low tissue culture passage isolates of wild mumps virus do not establish CNS infection after i.p. inoculation; after i.c. inoculation they cause limited though persistent infection with little acute mortality. The biological behavior of a highly passaged vaccine strain of mumps virus (Jeryl-Lynn) is more similar to NMV than to the wild strain in its behavior in the newborn hamster.

Adaptation, Biological↗
PubMed1977

Subacute measles encephalitis complicating Hodgkin's disease in an adult.

A progressive neurological illness characterized by myoclonus, motor and sensory deficits, and lethargy occurred in a patient with Hodgkin's disease and was fatal within two months. A focal inclusion cell encephalitis was demonstrated by immunohistological means to be due to measles virus. Measles encephalitis must be considered a potential opportunistic agent in the immune-compromised host.

Antibodies, Viral↗
PubMed1977

Adenine arabinoside in the treatment of progressive multifocal leukoencephalopathy: use of virus-containing cells in the urine to assess response to therapy.

Two patients with biopsy-proved progressive multifocal leukoencephalopathy (PML) were treated with near-maximal doses of adenine arabinoside (Ara-A), 18.6 and 20 mg per kilogram of body weight per day for 14 days. In both patients, clinical progression of the disease was correlated with an increase in the size of low-density lesions seen by computerized tomography. One of the patients was observed to excrete abnormal epithelial cells into the urine. These cells contained papovaviruslike particles, and JC virus was cultured from the urine sediment. The relative number of these abnormal cells declined during Ara-A treatment. Both patients died shortly after the conclusion of therapy without a change in the progression of the central nervous system disease. Systemic administration of Ara-A did not offer significant clinical benefit in the treatment of these 2 advanced cases of PML.

Aged↗
PubMed1977

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↗
PubMed1977

Mumps virus-induced hydrocephalus in hamsters. Ultrastructure of the chronic infection.

Newborn hamsters were inoculated intraperitoneally with neuroadapted mumps virus and sacrificed at intervals from days 3 through 50. Intracytoplasmic collections of nucleocapsids were found in ependymal cells and neurons on days 3 and 5 and virus formed at the plasma membrane of such cells by building. At closely apposed ventricular surfaces, mature particles appeared to form "bridges" between cilia of adjacent cells. Intracytoplasmic collections of nucelocapsids without evidence of maturation from cell surfaces could be found in ependyma for as long as 33 days. At the sites of apparent aqueductal occlusion, located in several animals, were found enlarged and distorted ependymal cells that did not define a lumen. The ependyma lining hydrocephalic lateral ventricles showed markedly attenuated cytoplasmic processes. Ependymal lined channels frequently coursed below the ventricular surface. Interstitial edema separated parenchymal elements of the underlying white matter. Conversion from an acute productive phase of infection to a chronic, nonproductive phase of infection in this model has ultrastructural correlates that appear to typify persistent paramyxoviral infections of brain.

Animals↗
PubMed1976

Progressive rubella panencephalitis.

A patient with progressive rubella panencephalitis developed initial symptoms of neurologic deterioration 12 years after childhood German measles. Progressive rubella panencephalitis should be considered in adolescents with progressive dementia attended by pyradmidal and cerebellar dysfunction.

Adult↗