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Biomedical subjects

D M Asher

Publications and source records attributed to D M Asher.

90 records · Page 5Linked to original sources

Cell fusion induced by scrapie and Creutzfeldt-Jakob virus-infected brain preparations.

Cell fusion was induced by brain extracts containing the scrapie virus and the virus of Creutzfeldt-Jakob disease. The assay involved quantitation of colony-forming ability in a double selection system, strandardized against fusion induced by Sendai virus. Correlation between the logarithm of virus dilution and the hybrid colony number gave similar curves for scrapie virus and Sendai virus. Fusion induction may explain some aspects of pathogenesis in these diseases and provide a potential in vitro assay.

Animals↗

Persistent shedding of adenovirus in urine of chimpanzees.

A new adenovirus, designated Pan 11, was isolated repeatedly from the urine of several chimpanzees for more than 1 year. One chimpanzee had chronic interstitial nephritis; the others were healthy. Most chimpanzees tested had neutralizing antibodies to Pan 11 virus in the serum; three people who worked with chimpanzees also acquired antibodies. Transplantable rhabdomyosarcomas developed in hamsters inoculated as newborns with Pan 11 virus.

Adenoviridae↗

Antibodies in urine of chimpanzees with chronic adenoviral viruria.

Many chimpanzees have naturally occurring chronic intermittent viruria with an adenovirus of a new type called Pan 11. Small amounts of neutralizing antibodies to Pan 11 adenovirus were found in the urine of chimpanzees. Urinary antibodies to adenovirus were mainly of the immunoglobulin G (IgG) class with some IgA antibodies also present. There was no neutralizing activity in urine against another adenovirus, Pan 9, which has been isolated from lymph nodes, but not from urine, of chimpanzees; however, sera of all chimpanzees had neutralizing antibodies to Pan 9 virus, some with titers similar to those of antibodies against Pan 11 virus. Antibodies reacting with simian cytomegalovirus by indirect immunofluorescence were found in sera of all chimpanzees tested and in two of six urines. There was no correlation between levels of antiviral IgG antibodies in serum and urine by immunofluorescence. These findings suggest that both IgG and IgA antibodies may be locally produced in response to viral infection of the urinary tract in primates.

Adenoviridae Infections↗

Hepatic amebiasis in spider monkeys.

In the past, investigators have been able to produce hepatic amebiasis in laboratory animals only by direct introduction of parasites into the liver or its vasculature, or by other artificial manipulations. A natural model of human visceral amebiasis has been lacking. We document an extensive outbreak of amebic dystentery which took place in a colony of spider monkeys; severe hepatic abscesses occurred in many animals. The spider monkey is highly susceptible to infection with Entamoeba histolytica and could provide a valuable model for the study of the pathogenesis of invasive amebiasis.

Animals↗

Precautions in medical care of, and in handling materials from, patients with transmissible virus dementia (Creutzfeldt-Jakob disease).

We have formulated a series of precautions to be observed in caring for patients with Creutzfeldt-Jakob disease and in handling their tissues. The virus resists inactivation by simple boiling in water. Also ineffective are 10 per cent formalin, 70 per cent alcohol and ionizing and ultraviolet radiation. Autoclaving for one hour at 121 degrees C and 20 psi inactivates the agent completely. Five per cent hypochlorite, 0.03 per cent permanganate, phenolics and iodine solutions are adequate disinfectants inactivating large infective doses of the virus. Special isolation wards for afflicted patients seem unwarranted. Workers exposed to infected saliva, nasopharyngeal secretions, urine or feces need to and should wash thoroughly with ordinary soap. Needles and needle electrodes should be autoclaved or incinerated and discarded. Demented persons should not be used for donations of blood or other tissues. Although precautions are necessary, the epidemiologic evidence does not suggest an unusual risk of Creutzfeldt-Jakob disease for medical workers.

Animals↗

Transmission of experimental kuru to the spider monkey (Ateles geoffreyi).

Clinical signs and pathological changes characteristic of kuru in man and experimental kuru in chimpanzees were observed in two spider monkeys, Ateles geoffreyi, after inoculation with brain tissue from a kuru-affected chimpanzee. The incubation period for one of the monkeys was 23 months, and 26 months for the other.

Animals↗

Induction in chimpanzees of antibodies inhibiting receptor-mediated cell fusion by HIV glycoprotein.

Cell fusion of HTLV-IIIB-infected EBV-transformed B cells and CD4+ T cells was inhibited by sera from eight of nine HIV infected chimpanzees. Syncytia formation was reduced by sixty percent relative to control after only 5 minutes of preincubation of the HIV infected cells with immune primate serum, indicating that these antibodies have high affinity for HIV protein on the surface of infected cells. Serum dilutions that blocked formation of syncytia irreversibly within 24 hrs also blocked expression of HIV antigens by the target CD4+ cells. Three of four animals inoculated with the LAV or HTLV-IIIB strain of HIV developed antibodies inhibiting CD4-dependent cell fusion by HIV glycoprotein (CFI-antibodies) 2-3 months after inoculation coincident with development of HIV specific IgG antibodies. Similar early CFI-antibody responses occurred in two second passage chimpanzees. In contrast, a chimpanzee infected with a third passage of LAV had a delayed CFI-antibody response, indicating that variants of HIV with divergent CFI epitopes did eventually emerge. Delayed development of CFI-antibodies (6-11 months after inoculation) relative to HIV specific IgG ELISA antibody was also seen in a chimpanzee on primary passage and a chimpanzee on second passage of HTLV-IIIB. No CFI-antibodies were detected in a chimpanzee following inoculation with human brain tissue, while antibodies to other structural proteins were recognized by immunoblotting. These results indicate that changes in CFI epitopes occur under immune pressure and that the appearance of CFI-antibodies depends on the time after infection and on the degree to which CFI epitopes of the inoculum strain diverge from those of the test strain.

Animals↗

Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease: background, evolution, and current concerns.

The epidemic of bovine spongiform encephalopathy (BSE) in the United Kingdom, which began in 1986 and has affected nearly 200,000 cattle, is waning to a conclusion, but leaves in its wake an outbreak of human Creutzfeldt-Jakob disease, most probably resulting from the consumption of beef products contaminated by central nervous system tissue. Although averaging only 10-15 cases a year since its first appearance in 1994, its future magnitude and geographic distribution (in countries that have imported infected British cattle or cattle products, or have endogenous BSE) cannot yet be predicted. The possibility that large numbers of apparently healthy persons might be incubating the disease raises concerns about iatrogenic transmissions through instrumentation (surgery and medical diagnostic procedures) and blood and organ donations. Government agencies in many countries continue to implement new measures to minimize this risk.

Animals↗

Pathogenesis of subacute spongiform encephalopathies.

The subacute spongiform encephalopathies include scrapie of sheep, transmissible mink encephalopathy, and kuru and Creutzfeldt-Jakob disease of man. These diseases are caused by filterable infectious agents with unique physical properties. The usual sources of infection in nature are not completely known. Epidemiological evidence suggests that the agents may enter the body through breaks in the skin and mucous membranes. Experimental studies of scrapie after subcutaneous inoculation demonstrated early replication of the agent in lymphoid tissues and later appearance in other organs; as the amount of agent in the central nervous system (CNS) increased, it decreased in or disappeared from lymphoid tissues. In preliminary studies of kuru and Creutzfeldt-Jakob disease, the infectious agents were regularly recovered from the brains of clinically-ill patients and experimental animals but only occasionally from organs outside the CNS. It remains to be seen if early events in the pathogenesis of the two human diseases, before the appearance of clinical signs, are similar to those in scrapie.

Adolescent↗

[The use of a primary astrocyte culture for modelling HIV neurological infection].

The article deals with the results of the experiment substantiating the in vitro model of HIV neuro-infection. In this work primary glial (astrocytic) tissue cultures obtained from normal human and animal (guinea pig) brain tissue were used. As revealed in this investigation, the following phenomena could be observed in human brain tissue monolayer culture, infected with HIV and subsequently subcultured: (a) the stimulation of tissue-cell growth; (b) the formation of multinuclear glial cells; (c) the presence of virus-specific proteins in astrocyte cytoplasm, detected by immunofluorescent and electrophoretic techniques; (d) the presence of HIV-1 DNA provirus in infected astrocytes. Cyto-destruction was not observed, reverse transcriptase activity was absent.

AIDS Dementia Complex↗