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Biomedical subjects

D M Asher

Publications and source records attributed to D M Asher.

At least 73 records · Page 4Linked to original sources

Extrathecal and intrathecal IgG response to the AIDS virus LAV/HTLV-III in experimental infection of chimpanzees.

Seven of seven chimpanzees inoculated with LAV/HTLV-III and three of three chimpanzee-to-chimpanzee passages seroconverted for LAV/HTLV-III as tested by ELISA and immunoblotting. Serum IgG reactivity to gag-gene products emerged between 3 and 6 weeks after inoculation, p24gag reactivity always reaching maximum titers first. Serum IgG antibodies to env-related proteins occurred 11-21 weeks after inoculation. Throughout the observation period (greater than 36 weeks), IgG reactivity to gag, pol, and env gene products persisted. Matched serum and cerebrospinal fluid (CSF) from three LAV/HTLV-III-infected chimpanzees were available in the chronic phase of infection and titers of viral antibody and albumin and IgG content were determined. By calculation of antibody/albumin indices, evidence was obtained for intrathecal synthesis of IgG antibodies to LAV/HTLV-III in one animal.

Acquired Immunodeficiency Syndrome↗

Abnormal proteins in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease.

We studied more than 300 cerebrospinal fluid proteins from 21 patients with Creutzfeldt-Jakob disease. We also examined cerebrospinal fluid from 100 normal controls and more than 400 patients with various neurologic disorders other than Creutzfeldt-Jakob disease. Four abnormal proteins that were identified in the patients with Creutzfeldt-Jakob disease were absent in the normal persons. Two of these proteins (Mr [relative molecular mass], 40,000; pl [isoelectric point], 5.7 and Mr 40,000; pl 5.9) were also present in some patients with multiple sclerosis, herpes simplex encephalitis, schizophrenia, Parkinson's disease, or Guillain-Barré or Behçet's syndrome. Two proteins (Mr 26,000; pl 5.2 and Mr 29,000; pl 5.1) were present in all patients with Creutzfeldt-Jakob disease and in 5 of 10 patients with herpes simplex encephalitis, but in none of the other control groups. A subsequent blinded study of these cerebrospinal fluid proteins from patients with Creutzfeldt-Jakob disease, Alzheimer's disease, Huntington's disease, multi-infarct dementia, parkinsonism dementia of Guam, or the specific dementia of the acquired immunodeficiency syndrome resulted in the ability to distinguish all cases of Creutzfeldt-Jakob disease from the other types of dementia. Although the identity and origin of the abnormal spinal fluid proteins are not yet known, these preliminary results suggest that their presence may help in the diagnosis of Creutzfeldt-Jakob disease.

Cerebrospinal Fluid Proteins↗

Diagnosis of Creutzfeldt-Jakob disease by Western blot identification of marker protein in human brain tissue.

We tested purified preparations of brain tissue from 39 patients with Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker syndrome, or kuru, and from 32 patients with a variety of nonspongiform degenerative diseases, with the use of Western blots against an antiserum to a similarly purified fraction made from scrapie-infected hamster brain. Positive reactions occurred in 81 percent of the 31 specimens from the patients with Creutzfeldt-Jakob disease (and in all of the 7 specimens that were stored frozen for less than one year), in 3 of the 4 specimens from the patients with kuru, in 3 of the 4 specimens from the patients with Gerstmann-Sträussler-Scheinker syndrome, and in none of the specimens from the patients with other neurologic degenerative disorders, including familial or sporadic Alzheimer's disease; dementia associated with myoclonus, motor neuron disease, or parkinsonism; and acquired-immunodeficiency-syndrome encephalopathy. Immunologic testing has thus begun to provide a useful and rapid adjunct to neuropathological examinations and animal-transmission experiments for the diagnosis of the spongiform encephalopathies.

Animals↗

Transmissible virus dementia: evaluation of a zoonotic hypothesis.

Creutzfeldt-Jakob disease (CJD) and kuru are subacute transmissible dementing encephalopathies characterized by spongiform changes in the brain. Scrapie is a similar slow viral encephalopathy which affects sheep, goats and certain other animals. Anecdotal reports suggest that Creutzfeldt-Jakob disease could be a zoonosis. To evaluate the possibility that CJD is acquired from animals, a case-control study was conducted on 26 well-documented CJD cases and 40 controls. Data were collected on exposure to animals through occupations, hobbies, sports and pets. An excess exposure to certain animals was noted among the patients compared to controls in relation to occupation (deer, monkey, squirrel; odds ratio (OR) = 8.9; p less than 0.10) and hobbies (deer, OR = 9.0; rabbit, OR = 6.0; p less than 0.05). Similarly, exposure to animal organs was significantly greater in the CJD group (OR = 20.9; p less than 0.005). Statistically significant increased exposure to sheep or goats was not found among the patients. However, since spongiform encephalopathy has a wider host range than sheep and goats, the increased exposure to certain other animals suggests that a zoonotic source for CJD should be further explored.

Adult↗

Post-encephalitic epilepsy and arbovirus infections in an isolated rainforest area of central Liberia.

Among a population of 4.436 Bassa, Kpelle and Mano people in the Gbawein and Wroughbarh Clan region of Grand Bassa Country, Liberia, 123 cases of epilepsy could be documented. In 38% of these cases infections involving the central nervous system precipitated the onset of seizures. Sera from 67 epilepsy patients, 50 direct healthy relatives and 22 geographically matched controls were tested for antibodies to 16 arboviruses of the Togaviridae and Bunyaviridae known to occur in Africa. Antibodies to arboviruses were found in 16.5% of the epilepsy patients, 36% of the mostly older family members, and in 22% of the controls. Males and females were equally affected as were the different clans and language groups. Although meningoencephalitis with sequelae, like seizures, are known to result from arbovirus infections, no evidence for a correlation between epilepsy in this are of Central Liberia and previous arbovirus infection could be established.

Adolescent↗

Hemorrhagic fever virus infections in an isolated rainforest area of central Liberia. Limitations of the indirect immunofluorescence slide test for antibody screening in Africa.

Serum samples from 119 healthy individuals and 106 epilepsy patients inhabiting Grand Bassa County, Liberia, were tested for antibodies to hemorrhagic fever viruses (HFV) by indirect immunofluorescence. E6 Vero cells infected with Lassa fever virus (LAS), Rift Valley Fever virus (RVF), Congo Hemorrhagic Fever virus (CON), Marburg virus (MBG) and the Ebola (EBO) virus strains Mayinga (May) and Boniface (Bon) were used as antigen. To obtain reproducible and specific test results sera had to be absorbed extensively with uninfected E6 Vero cells, tested for reactivity to both virus infected and uninfected E6 Vero cells and read "blindly" by two independent observers. Antibodies to EBO were shown to be highly prevalent (13.4%) in the population of this rainforest area, while prevalences of antibodies to LAS (1.3%), RVF (0.4%) and MBG (1.3%) were much lower. No correlation between past HFV infection and post-encephalitic epilepsy or other reported febrile illnesses could be established.

Adolescent↗

A case-control study of Creutzfeldt-Jakob disease. Dietary risk factors.

The mode of natural transmission of Creutzfeldt-Jakob disease remains unknown. In a case-control study conducted in 1981-1983 to evaluate possible dietary and other sources of the disease, 26 cases were ascertained in the mid-Atlantic region of the United States, 23 of which were obtained from accumulated records of the Laboratory of Central Nervous System Studies of the National Institutes of Health. Controls included 18 family members and 22 hospital-matched individuals (total sample size, 66). An increased consumption among patients was found for roast pork, ham, hot dogs (p less than 0.05), roast lamb, pork chops, smoked pork, and scrapple (p less than 0.1). An excess consumption of rare meat (p less than 0.01) and raw oysters/clams (p less than 0.1) was also reported among the patients. Liver consumption, among organ foods, was greater (p less than 0.1) among the cases. If Creutzfeldt-Jakob disease is acquired through ingestion of foods containing the agent, then the food items identified may be among those which need to be evaluated more intensively. Larger case-control studies with more focused dietary questions are warranted.

Adult↗

Attempts to implicate viruses in myasthenia gravis.

We investigated the hypothesis that a persistent viral infection of the thymus gland might trigger the autoimmune disease myasthenia gravis (MG). Thymus glands of nine patients with recent onset of MG were studied by a variety of techniques to detect the presence of occult viruses. No evidence of viral infection was found.

Adolescent↗

Evidence for and against the transmissibility of Alzheimer disease.

Nonhuman primates were inoculated intracerebrally with brain tissue from 52 patients with confirmed Alzheimer disease (AD) in order to investigate the possibility of an infectious etiology. Animals inoculated with brain tissue from two patients with familial AD developed a spongiform encephalopathy that was indistinguishable from Creutzfeldt-Jakob disease (CJD). Seventeen other cases of AD on test for more than 50 months failed to produce similar changes, and 33 cases have not been incubating for a sufficient period of time to ascertain the presence of a transmissible agent. The initial transmission of spongiform encephalopathy with brain tissue from the two familial cases of AD has not been reproduced and the association between AD and an infectious agent has not yet been demonstrated with any reasonable degree of certainty. The frequent overlap of clinical symptoms of AD and CJD, and the occurrence of cases of CJD and AD in the same families indicate the need for continuing research on the relationship between the two diseases.

Alzheimer Disease↗

Creutzfeldt-Jakob disease: patterns of worldwide occurrence and the significance of familial and sporadic clustering.

The worldwide epidemiology of Creutzfeldt-Jakob disease (CJD) is presented from an analysis of 1,435 patients. In the United States, the average annual mortality rate is at least 0.26 deaths per million. Temporal-spatial clustering of cases was not found in the United States, but reports from other countries indicate that such clustering does occur. Fifteen percent of the cases were of the familial type, suggesting a genetic susceptibility to infection. Iatrogenic transmission by corneal transplantation and neurosurgical operations has occurred, and the possibility is raised that previous surgery or preexisting neurological operations has occurred, and the possibility is raised that previous surgery or preexisting neurological disease may be associated with an increased risk of developing CJD. It remains to be determined whether the virus of CJD is maintained only by patient-to-patient transmission, has a zoonotic reservoir such as scrapie, or causes widespread latent infection of man that is occasionally activated.

Adolescent↗