Search PubMed⌕ Search

Biomedical subjects

H R Brown

Publications and source records attributed to H R Brown.

At least 55 records · Page 3Linked to original sources
PubMed1983

Pathogenesis of viral encephalitis: demonstration of viral antigen(s) in the brain endothelium.

One of the enigmas in the pathogenesis of inflammation is why the white cells adhere to the endothelium. In trying to define the pathogenic mechanism, we carried out experiments on ferrets infected with an SSPE strain of measles virus. Using immunoperoxidase labeling techniques, viral antigens were demonstrated on the luminal surface and in the cytoplasm of endothelial cells, irrespective of the presence or absence of inflammatory changes. The degree of inflammation corresponded well with antibody titer. These data suggest that the viral antigen in the endothelial cells is the site of interaction between these cells and sensitized lymphoid cells.

Animals↗
PubMed1983

Assembly of proteolytically cleaved tubulin.

Conditions have been found for limited proteolysis of purified tubulin, in which 70-90% of the molecules are cleaved at one or two sites. Thermolysin and chymotrypsin cleave the alpha and beta subunits, respectively, at single sites. Trypsin cleaves the alpha subunit at two sites. The chymotrypsin site and one of the trypsin sites are apparently inaccessible on assembled microtubules. The different samples of proteolyzed tubulin were all fully competent to assemble in a buffer containing 1 M sodium glutamate. In another buffer (50 mM morpholinoethanesulfonic acid, 3.4 M glycerol) tubulin digested by thermolysin assembled as well as native tubulin, but samples digested by chymotrypsin or trypsin would not assemble even at high protein concentrations.

Binding Sites↗
PubMed1983

Presence of oligoclonal immunoglobulin G bands and lack of matrix protein antibodies in cerebrospinal fluids and sera of ferrets with measles virus encephalitis.

Young adult ferrets were immunized with measles vaccine and 5 to 6 weeks later inoculated intracerebrally with Vero cells persistently infected with cell-associated strain D.R. of measles virus isolated from a patient with subacute sclerosing panencephalitis. Of nine ferrets which survived the infection for 3 weeks or longer, five showed neurological signs. At the time of death they had widespread inflammation in their brains, and cell-associated virus was isolated from three ferrets sacrificed from 5 weeks to 7 months after inoculation. Four ferrets did not develop clinical signs, but two of these had mild inflammation in the brain 7 months and 2 1/2 years after inoculation, respectively. Cerebrospinal fluids drawn by cisternal puncture from infected ferrets at the time of sacrifice had neutralizing titers against measles virus similar to the titers found in sera, but antibody against the measles virus matrix protein was not detectable. Cerebrospinal fluid showed increased immunoglobulin G (IgG) and had distinct measles virus-specific oligoclonal IgG bands. The intensity of the bands correlated with the neutralizing titers of the fluids. These results confirm and extend earlier findings and indicate that persistent measles virus infection in ferrets is similar to human subacute sclerosing panencephalitis and can be used to study certain aspects of persistent brain infections leading to subacute encephalitis.

Animals↗
PubMed1980

Immunolabeling of SSPE and wild-type measles viruses in ferret brain cell culture.

Immunocytochemical studies using horseradish peroxidase labeled antibody were undertaken in an attempt to determine whether there are detectable antigenic differences which correlate with the biological properties of differences which correlate with the biological properties of different strains of SSPE and wild-type measles virus grown in ferret bran cell cultures. The rabbit anti-measles hyperimmune serum used in this experiment contained antibodies to all the measles virus proteins when tested by immunoprecipitation. When cells infected with the wild-type measles or productive SSPE virus strains were treated with this serum, heavy deposits of reaction product were seen on the cell membrane and virion envelope. When SSPE serum which contained relativly little antibody to the M protein was applied, a clear unlabeled area was evident just beneath the surface label. Cells infected with the non-productive SSPE strains were labeled by both sera in a spotty or discontinuous pattern on the outer surface of the cell membrane. The differences in membrane labeling seem to reflect differences in the expression of viral membrane proteins by the various SSPE and measles virus strains.

Animals↗
PubMed1978

Comparison of wild-type and subacute sclerosing panencephalitis strains of measles virus. Neurovirulence in ferrets and biological properties in cell cultures.

The neurovirulence of two wild type (wt) and seven Subacute Sclerosing Panencephalitis (SSPE) measles virus strains was tested in young adult ferrets by intracerebral (IC) inoculation of infected Vero cell suspensions. Wt strains Edmonston and Woodfolk and SSPE strains Mantooth, Halle, and LEC-S did not produce a detectable encephalitis in the ferrets, but caused a significant formation of serum antibodies against measles virus. SSPE strains LEC, IP-3, Biken, and D.R., on the other hand, were all neurovirulent in ferrets, particularly strain D.R. which caused an acute encephalitis in all inoculated animals. Strain Biken was of particular interest since it caused a subacute encephalitis in four of seven ferrets. The subacute encephalitis was characterized by a long incubation time, persistence of virus in the brain for at least 8 mo, widespread inflammatory lesions, and production of measles virus specific IgG in the brain. A study of the biological properties of the various measles virus strains showed that wt strains Edmonston and Woodfolk and SSPE strains Mantooth, Halle, and LEC-S produced free virus particles in significant titers both in Vero and ferret brain (FB) cultures. Cytopathic effect (CPE) with cell-fusion was marked in Vero cultures, whereas only minimal CPE and no cell-fusion were observed in the FB cultures. SSPE strains LEC, IP-3, Biken, and D.R., on the other hand, were mostly cell-associated in Vero and FB cultures, although atypical cell-free particles were produced by strains Biken and IP-3. All four strains showed cell-fusing activity in FB cultures, particularly strain D.R., which was the only strain that spread more actively by fusion in FB than in Vero cultures. The results are discussed in relation to the neurovirulence of the various measles virus strains in adult ferrets. Pronounced cell-fusing activity in FB cells and cell-association with minimal or no production of cell-free virus seem to be essential to establish a brain infection in the animals.

Animals↗
PubMed1977

Antibody in SSPE serum and brain igG against measles virus smooth nucleocapsids detected by immunoelectron microscopy.

SSPE patients characteristically have high complement-fixing (CF) and neutralizing (N) antibody titers against measles virus in their sera, CSF, and brain. However, using SSPE patients' sera, the immunoperoxidase (IP) labeling of smooth nucleocapsids in SSPE or measles virus infected Vero cells or measles virions has not been achieved using conventional EM fixatives. Using the periodate-lysine-paraformaldehyde (PLP) fixative developed by McLean and Nakane (1974), and the indirect IP technique, antibodies against smooth nucleocapsids in SSPE and measles virus infected Vero cell cultures have been detected in serum from SSPE patients and normal individuals with high measles antibody titers.

Adolescent↗
PubMed1977

Ultrastructural and histological studies of brains of ferrets inoculated with subacute sclerosing panencephalitis: similarities to human disease.

Similarities to human subacute sclerosing panencephalitis (SSPE) were revealed in a study of the brains of ferrets inoculated with a cell associated measles virus originally isolated from an SSPE patient. The similarities were greatest in animals that showed neurological signs 3-4 months after inoculation and had high titers of neutralizing antibodies against measles virus. These included dense core particles, nuclear bodies, alterations of basement membranes of small blood vessels, plasma cells, distorted myelin, and rod-like structures in some nuclei. Other abnormalities seen were Hirano bodies, tubular aggregates in cisternae of endoplasmic reticulum and clusters of cytoplasmic tubules. No cells containing viral inclusion bodies were observed by electron microscopy but cell cultures of the brains of these animals always yielded abundant measles virus nucleocapsids in typical SSPE multinucleated syncytia. These findings suggest that the ferret is a suitable animal model for the study of the pathogenesis of SSPE.

Animals↗
PubMed1976

Synaptosomal adenosine triphosphatase (ATPase) inhibition by organophosphates.

Chicken spinal cord adenosine triphosphatases (both Na+, K+ stimulated and ouabain insensitive) were inhibited by tri-o-tolyl phosphate (TOTP, a neurotoxic organophosphate which is not a cholinesterase inhibitor) and mevinphos (a non-neurotoxic compound but inhibitor of cholinesterases). The inhibition was concentration and time dependent, with an initial rapid drop in activity followed by a gradual exponential decline.

Adenosine Triphosphatases↗
PubMed1976

Immunoperoxidase staining of simple nuclear bodies in sclerosing panencephalitis (SSPE) by antiserum to Measles nucleocapsids.

Nuclear bodies have been found with great consistency in brain tissue from patients with subacute sclerosing panencephalitis (SSPE). There has been controversy as to the significance of these structures and their relationship, if any, to the disease. In this study, a non-productive, cell-associated strain of SSPE measles virus grown in tissue culture on Vero cells showed the continued presence of nuclear bodies, frequently in close association with the continued presence of nuclear bodies, frequently in close association with the SSPE measles virus nucleocapsids. Immunoperoxidase (I-P) staining with specific antiserum against measles virus nucleocapsids was done. The resultant positive labeling of the nuclear bodies demonstrates that they contain measles virus antigen and suggests that the nuclear bodies play a role in the development of the measles virus nucleocapsids of SSPE.

Antigens, Viral↗
PubMed1976

A non-productive subacute sclerosing panencephalitis (SSPE) virus of human and ferret: an ultrastructural study.

A non-productive syncytiogenic measles virus isolated from the brain of an SSPE patient was grown on Vero cells. The ultrastructure of the infected syncytia was studied by electron microscopic and immunoperoxidase techniques. It was compared with the isolate of the virus after passage in ferrets, the Edmonston strain of wild measles virus and the Halle productive strain of SSPE, all on Vero cells. The immunoperoxidase labeling of the cell membranes of the Edmonston measles virus infected cells was very heavy and uniform. In contrast, the labeling of the non-productive SSPE infected cells was clearly discontinuous. In the latter, there was a preponderance of intranuclear over cytoplasmic nucleocapsid formation, whereas cytoplasmic nucleocapsids were prevalent in the virion-producing strains. Many similarities between Vero cells infected with the wild measles virus and the Halle strain of SSPE were observed, although differences between this SSPE strain and strains reported by others were noted.

Adolescent↗