Publications

the physico-chemical nature of the scrapie agent.		1976	8342
slow encephalopathies, inflammatory responses and arachis oil.	there is much interest in the possibility that diets rich in some plant oils may be of prophylactic and curative value in certain clinical conditions. this is generally attributed to the immunosuppressive effects of polyunsaturated fatty acids. arachis (peanut) oil injections can increase the incubation period of experimental scrapie in mice. in the late 1950s several workers showed that arachis and some other oils contained very potent anti-inflammatory components quite apart from the polyunsat ...	1975	47424
letter: interspecies transmission of scrapie-like diseases.		1975	54832
a personal view of scrapie research.		1977	68237
neurophysin in the brain and pituitary gland of normal and scrapie-affected sheep--ii. its occurrence in the cerebellum in dystrophic axon terminals with lysosome-lipofuscin accumulation: a possible anomaly of neuronal sulphur-protein metabolism.		1977	72365
relation between carp (multiple-sclerosis associated) agent and multiple sclerosis.	it is suggested that the carp (multiple-sclerosis associated and scrapie associated) agents may be the v-r.n.a. form of slow (d.n.a.) viruses which are the aetiological agents of the two diseases.	1976	73745
structure-function correlation in mammalian neurosecretion.		1978	77853
reduced choline-acetyltransferase activity in scrapie mouse brain.		1978	79111
antiviral compound effective against experimental scrapie.		1979	89602
evidence that the transmission of one source of scrapie agent to hamsters involves separation of agent strains from a mixture.	a previous paper (kimberlin & walker, 1977) described an experimental model of scrapie in hamsters in which the incubation period decreased progressively over the first 4 passages before becoming stable at the 5th and subsequent passes. studies have been made of some of the agent strains present in brains taken from the 2nd, 3rd, 4th and 6th hamster passes. the results indicate the presence of at least two strains of agent at the 3rd passage level. one of these (431k) is highly pathogenic for mi ...	1978	96212
evidence for an essential dna component in the scrapie agent.		1978	99663
effect of different gradient solutions on the buoyant density of scrapie infectivity.		1978	99747
studies of the lymphoreticular system in the pathogenesis of scrapie: the role of spleen and thymus.		1978	101558
resistance of scrapie agent to decontamination.		1978	101846
partial purification and evidence for multiple molecular forms of the scrapie agent.	a procedure for the partial purification of the scrapie agent from mouse spleen was developed based on its sedimentation profile. differential centrifugation and detergent treatment with sodium deoxycholate yielded a fraction designated "p5" which was enriched for scrapie infectivity approximately 20-fold with respect to cellular protein. the p5 fraction was devoid of cellular membranes but heavily contaminated with ribosomes as judged by electron microscopy. on centrifugation of the fraction p5 ...	1978	102338
scrapie: the lesson we must learn.		1978	103019
pathogenesis of scrapie: agent multiplication in brain at the first and second passage of hamster scrapie in mice.	the intracerebral (i.c.) injection of mice with a particular source of hamster passaged scrapie produced disease after an incubation period of 325 +/- 6 days (mean +/- s.e.). the incubation period at the second i.e. passage in mice was reduced to 149 +/- 2 days. studies were made of the dynamics of agent replication at 1st and 2nd passages in mice. at first passage, there was a 'zero phase' lasting about 175 days, when no infectious agent was detected in brain (or spleen), followed by a period o ...	1979	103999
unusual resistance to ionizing radiation of the viruses of kuru, creutzfeldt-jakob disease, and scrapie.	the titers of several preparations of kuru. creutzfeldt-jacob disease, and scrapie viruses were reduced by only 1/10th or less by high doses of gamma radiation of 50 kgy and by only 1/10th-1/1000th or less for 200 kgy. this unusual radiation resistance of the two human viruses further links them with the scrapie virus and suggests that the genetic information of all three viruses is considerably smaller than that of any other known viruses of mammals.	1978	104301
the scrapie agent: is it a viroid?		1979	104387
the scrapie agent: evidence against its dependence for replication on intrinsic nucleic acid.	exposure of the scrapie agent to u.v. light at various wavelengths has shown that light of 237 nm is 4 to 5 times as effective in inactivating it as 'germicidal' wavelengths (250 to 270 nm); whereas with systems that depend on rna or dna for function, inactivation is most effective by wavelengths in the germicidal range and there is a minimum of response in the wavelength region round 240 nm. the action spectrum for the scrapie agent is reminiscent of the absorption spectrum for purified bacteri ...	1978	106090
evidence for the low molecular weight nature of scrapie agent.		1979	107457
slow infections with unconventional viruses.		1978	108233
[cellular fusion induced in vitro by the mouse scrapie agent].	a method is described to demonstrate and measure the cell-fusion in vitro induced by viruses. this technique has been established using sendai virus. it has been used to study the fusing ability of the scrapie agent which is responsible of a slowly progressing spongiform encephalopathy in mice. in vero cells, the scrapie agent induces a fusion which appears slowly and remains moderate. this test can help to detect the human spongiform encephalopathies.	1979	111844
the discovery of a particle unique to brain and spleen subcellular fractions from scrapie-infected mice.		1979	113498
evidence for hydrophobic domains on the surface of the scrapie agent.		1978	117582
pathogenesis of mouse scrapie: dynamics of agent replication in spleen, spinal cord and brain after infection by different routes.		1979	120379
familial and sporadic chronic neurological degenerative disorders transmitted from man to primates.		1975	125030
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 ...	1976	129025
properties of the scrapie agent-endomembrane complex from hamster brain.	subcellular fractionation of scrapie-infected hamster brain indicated the association of the scrapie agent with a component of the endomembrane system. characterization by equilibrium density gradient centrifugation, electron microscopy, and marker enzymes suggested a primary association with rough and smooth endoplasmic reticulum and a possible incorporation into the plasma membrane. dna polymerase activity demonstrated a direct correlation with regions of scrapie activity from the gradient fra ...	1976	131866
[discovery of viroids and possible relationship with human and veterinary medicine].	the researches of diener and co-workers and those of the semancik's group, have recently established that some plant diseases, such as potato spindle tuber, citrus exocortis disease and chrysanthemum stunt, are caused by a new class of pathogens, named viroids. these are the smallest known agents (they are smaller than viruses) having a molecular weight of ca 10(5) daltons, and composed of a highly structured rna, rich in guanine-cytosine base pairs without a capsid. little is known about the or ...	1975	132907
recent data on the properties of the viruses of kuru and transmissible virus dementias.		1975	134597
unconventional viruses and the origin and disappearance of kuru.		1977	142303
classic slow virus diseases.	two human disease, kuru and creutzfeldt-jakob disease, and two animal diseases, scrapie and mink encephalopathy, comprise the group designated the subacute spongiform encephalopathies. studies on these four classic conditions have generated a new philosophy, new concepts, and new technology that provide a basis for the study of chronic diseases and latent infections of man and animals. these aspects are discussed more broadly and in variable detail in the references listed on the following page.	1977	143298
mendelian inheritance or transmissible agent? the lesson kuru and the australia antigen.		1977	146739
persistent or slow viral infections and related diseases.	the discovery of persistent transmissible agents by veterinarians has led to striking advances in the infectious cause of neuropathies of human beings. there is evidence for persisting infection in congenital rubella and the herpes group of viruses including cytomegalovirus infections. hepatitis types a and b are candidates for inclusion in the category of persisting viral infections. the rubeola or measles virus is established as a persistent virus which causes elevated antibodies in the serum ...	1975	165638
newer knowledge in comparative virology--its contribution to human health research.	like other comparative sciences, and despite its recent beginning comparative virology has already contributed useful applications and observations to human health research. teachings derived from the study of marek's disease found application in that of burkitt's lymphoma, and may lead to a possible vaccine against the human disease. equally useful information came from the study of canine distemper in the development of a chorio-allantoic membrane attenuated measles vaccine, and in our knowled ...	1975	167504
our present knowledge of the pathology of dementias.		1975	172773
the occurrence of vacuolated neurons in the brains of hamsters affected with subacute sclerosing encephalitis following measles or langat virus infection.	hamsters infected by the intranasal route with either hamster adapted langat virus passaged at least 10 times in hamsters and the hnt strain of measles virus passaged 149 times in hamsters, developed subacute sclerotic lesions in the pyriform cortex, and beginning from 2 months after infection, were accompanied by neuronal vacuolation with ballooning of the cytoplasm, especially in parts of the brain in close proximity of the sclerotic lesions. the vacuolated neurons resembled those seen in scra ...	1975	173381
some final comments on visna-maedi aleutian disease and scrapie.		1976	182561
slow viral diseases of the central nervous system: transmissibility vs. communicability.		1977	201420
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 vit ...	1978	208080
sedimentation characteristics of the scrapie agent from murine spleen and brain.	sedimentation profiles of the scrapie agent in extracts of murine spleen and brain were determined by analytical differential centrifugation. infectivity profiles of the agent from the two tissues were similar. sedimentation of the agent was not substantially altered by detergent treatment with sodium deoxycholate. in the presence of detergent, centrifugation at an omega2t value of 3.0 x 1010 rad2/s in a fixed-angle rotor sedimented 90% of the agent. comparative studies with radioisotopically la ...	1978	214106
genetics of resistance of animals to viruses: i. introduction and studies in mice.		1978	219668
slow viruses and chronic disease of the central nervous system.	although recognized since the 1930s, slow infections have only recently received considerable attention. there are three types, group a (related to the type c rna viruses), group b (bizarre agents such as scrapie and kuru) and group c (viruses such as measles which normally produce acute infections but which are behaving here in an unusual fashion). these viruses are only united in that they produce disease with excessively long incubation periods. many slow infections result in neurological dis ...	1979	223140
[in vitro fusion ability of agents causing slow diseases of the central nervous system].	the authors study cell fusion in vitro induced by two kinds of slow viruses : visna virus of sheep and scrapie of mouse and creutzfeldt-jakob disease of man agents. cell-fusion induced by visna virus is either slow and late occuring (fusion from within) or early and rapid (fusion from without) according to experimental conditions. whereas, cell-fusion induced by spongiform encephalopathies agents is only of slow appearance, looking an endogenous phenomenon.	1979	226238
slow viral infections.		1979	231926
scrapie: a point of view.		1977	275684
scrapie- the risks in perspective.		1977	276740
scrapie-a point of view.		1977	276749
scrapie: a point of view.		1977	276750
scrapie scruples.		1978	278924
acceleration of scrapie in mice by target-organ treatment with interferon inducers.	interferon inducers were used in the target-organ treatment of scrapie in mice. intracerebral treatments began 24 hr prior to intracerebral inoculation of 10(4.8) ld50 of the chandler strain of scrapie agent. the treatments included 30 and 0.3 microgram poly(i:c) given weekly 9 times, 45 microgram statolon given biweekly 7 times, or 1.5 ha units of sendai virus given biweekly 6 times. all treatments except the lower dose of poly(i:c) accelerated death in scrapie-affected mice. compared to saline ...	1977	280156
suppression of polyclonal b cell activation in scrapie-infected c3h/hej mice.	a consistent modification in b lymphocyte activation has been observed 1 month after infection of c3h/hej mice with scrapie. the mitogenic response to lipopolysaccharide of splenocyte cultures from experimental mice was reduced 30 to 60% as compared to controls. this reduction in mitogen responsiveness was transient but coincided with the onset of detectable splenomegaly and with the reported recovery of maximum yield of infectious scrapie agent in the spleen. the dna synthetic response to lipop ...	1978	307027
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 disinfec ...	1977	335248
[spongy encephalopathy in man and animals (author's transl)].	with reference to new points of view on the pathogenesis and nature of diseases showing microscopically perceptible spongy features as the main lesion in haemalum-eosin-stained sections of particular portions fo the central nervous system in various animals and man, important findings reported in the literature on the subject are reviewed.	1977	335565
transmission of creutzfeldt-jakob disease with scrapie-like syndromes to mice.		1978	342977
transmission of agent of creutzfeldt-jakob disease.		1978	346155
slow virus infections of the nervous system. 2. diseases due to unconventional viruses.		1978	349304
[method of electrophoretic mobility of macrophages and its use in clinical immunology].	a test of measurement of the electrophoretic mobility of macrophages (emm) is used for detection of the product secreted by the sensitized lymphocytes after the contact with the antigen. thus, by reduction of the macrophage mobility it is possible to assess the sensitization level of the lymphocyte population under study. this offers a possibility of using this test for the diagnosis of some infectious diseases, for provisional diagnosis of malignant growth, and also of destructive affections of ...	1978	352059
virus-induced subacute slow infections of the brain associated with a cerebellar-type ataxia.		1978	367118
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 transpl ...	1979	371520
transmission of chronic spongiform encephalopathy with kuru plaques from humans to small rodents.	an unusual case of spongiform encephalopathy was transmitted directly from a human to rats and mice. after serial passages, incubation periods were shortened to about six months in rats and four months in mice. clinical symptoms were similar in rats and mice, including ruffled fur, arched back, bradykinesia, and hind limb paralysis. pathologically, a spongy state, proliferation of astrocytes, and neuronal changes were observed. electron microscopic observation of the parietal cortex of rats and ...	1979	382976
creutzfeldt-jakob disease in france: iii. epidemiological study of 170 patients dying during the decade 1968--1977.	systematic search for creutzfeldt-jakob disease (cjd) in france yielded a total of 170 patients dying between 1968 and 1977. the overall annual mortality rate from cjd for france was 0.32 case per million persons, with by far the highest rate (1.33 cases per million) in the most densely populated parts of paris. a highly significant correlation between population density and the mortality rate of cjd in the paris urban agglomeration was consistent with the hypothesis of human-to human disease tr ...	1979	391142
[creutzfeldt-jacob disease in continental france. retrospective study from 1968 to 1977].	during the decade 1968-1977, 170 cases of creutzfeldt-jakob disease were found in france. the clinical features of 124 neuropathologically-verified cases are summarized and a multi-factor analysis performed to obtain the most frequent combinations of signs and symptoms. certain exceptional features are discussed. the annual mortality rate during this period was 0.32 cases per million for the whole of france, and 0.69 cases per million for the paris metropolitan area. preliminary totals for 1978 ...	1979	395612
failure of fluorocarbon treatment to affect sensitivity of scrapie agent to ultraviolet light.		1977	402398
characteristics of a short incubation model of scrapie in the golden hamster.	repeated passage of the "chandler" strain of scrapie in female golden hamsters using the intracerebral route of inoculation reduces the minimum incubation period to 60 days, about half of the minimum incubation period so far found in any of the mouse models of scrapie. the infectivity titres in brain in the clinical stage of the disease are considerably higher (greater than 8-0 -log10 ld50 i.c. units/0-05 g) than those found in mouse scrapie. the biological characteristics of this model of hamst ...	1977	402439
latent form of scrapie virus: a new factor in slow-virus disease.	scrapie is an unusual slow-virus disease of sheep which is very much like kuru and creutzfeldt-jakob disease, both fatal, slow neuological diseases of man. in mice, scrapie usually has an incubation period of about 6 months. intraperitoneal inoculation of virus particles into newborn mice caused no disease, and there was no detectable virus replication for 1 year, but high titers of scrapie were present in the spleen and brain at 18 months. virus replication occurred in mice injected from 4 days ...	1977	404706
search for a specific marker in the neural membranes of scrapie mice: a freeze-fracture study.		1977	405528
[slow infections: development of the problem and classification of the agents].		1977	408993
[slow virus infections].		1977	411966
sedimentation properties of the scrapie agent.	the sedimentation behavior of the scrapie agent in homogenates of spleen from infected mice has been determined. approximately 90% of the scrapie agent was sedimented at an omega2t value of 3 x 10(10) rad2/sec in a fixed-angle rotor. sedimentation of the agent was not substantially affected by sonication or by treatment with the detergent sodium deoxycholate. the sedimentation profiles of the scrapie agent were similar to those observed for free polyribosomes, but differed from those exhibited b ...	1977	412193
slow infections of the nervous system.		1978	415527
slow virus e malattie croniche del sistema nervoso centrale.	the purpose of this report was to detect whether some subacute or chronic human neurological diseases are significantly associated with traditional virus like papovavirus and paramixovirus and non conventional agents (scrapie-like) or non classified (multiple sclerosis associated agent or msaa). in this connection for m.s. the data concerning the ethiological factors paramixovirus or mssa are presented and discussed and it is hypothesized the virus mechanism in the pathogenesis of m.s.	1978	415749
immunological assessment of ageing: emergence of scrapie-like antigens.	certain morphological similarities between scrapie--a naturally occurring disease of sheep, long looked upon as a paradigm of 'slow infections'--and the ageing process in normal animals led to a study of the development of new antigens both in scrapie-affected animals and in normal mice and humans. it was found that with advancing age new antigen(s) identical with, or similar to, those occurring in scrapie (where the time co-ordinate of aging in the brain seems foreshortened) make their appearan ...	1978	416662
membrane-free scrapie activity.	determinations of scrapie activity in subcellular fractions from infected hamster brains through the asymptomatic and symptomatic course of infection revealed the presence of substantial amounts of scrapie infectivity in the 100,000 x g supernatant fractions, indicating that association with physically discernible membrane structures is not necessary for the transmission of the scrapie agent. an increase of scrapie infectivity in the 100,000 x g supernatant fractions after vigorous homogenizatio ...	1978	417194
aetiology and genetic control of natural scrapie.		1979	423984
[naked deoxyribonucleic acid viroids as the causative agents of neuropathies?].		1979	431739
immunoglobulin g concentrations in the sera of herdwick sheep with natural scrapie.		1979	528692
ocular effects of scrapie agent in hamsters: preliminary observations.	scrapie is caused by one of a group of so-called slow viruses responsible for the subacute spongiform encephalopathies. in the present study, young hamsters were inoculated intracerebrally with hamster-adapted scrapie agent. at termination, all inoculated animals showed signs and central nervous system pathology compatible with scrapie infection. the eyes appeared well developed grossly, but histologically the retina and optic nerve were abnormal. there were varying degrees of thinning of the re ...	1977	557461
virus-like particles from both control and scrapie-affected mouse brain.		1977	559944
pathogenesis of mouse scrapie: effect of route of inoculation on infectivity titres and dose-response curves.		1978	563870
mitogenic stimulation of the host enhances susceptibility to scrapie.		1978	564461
the syrian hamster as a model for the study of slow virus diseases caused by unconventional agents.		1978	565302
histopathological and enzyme histochemical changes in experimental semliki forest virus infection in mice and their relevance to scrapie.		1978	566770
plasmalogenase is elevated in early demyelinating lesions.	plasmalogenase catalyzes the hydrolysis of ethanolamine plasmalogens to long-chain aldehydes and 2-acyl-sn-glycero-3-phosphoethanolamines. during development, plasmalogenase activity parallels myelination. the enzyme is most concentrated within oligodendroglial cells and is absent from myelin. the normal function of plasmalogenase in white matter may be related to its specificity for plasmalogens that contain most of the thromboxane and prostaglandin precursors. plasmalogenase activities are ele ...	1978	567935
mitogen stimulation of splenocytes from mice infected with scrapie agent.	spleen weights and mitogen responsiveness of splenocyte cultures from scrapie agent-infected and control-inoculated mice were compared over two-month periods following inoculation. splenocytes from swiss, c57b1, and balb/c mice were stimulated with the t (thymus-derived) cell mitogens phytohemagglutinin or concanavalin a, the b (bone marrow-derived) cell mitogen bacterial lipopolysaccharide, or pokeweed mitogen, a stimulator of both t and b cells. although significant splenomegaly was associated ...	1978	568156
experimental scrapie in mice: ultrastructural observations.	scrapie, kuru, and creutzfeldt-jakob disease are characterized by a similar spongiform pathology, prolonged incubation periods, and an agent with unique physical, chemical, and biological properties. swiss mice were inoculated with the scrapie agent and sacrificed three to five months later for light and electron microscopy. at three months, small vacuoles were seen within the neuropil of the cerebral cortex and basal ganglia. by the fifth month these vacuoles had increased in number and size an ...	1978	568909
experimental production of scrapie-resistant swaledale sheep.		1977	605475
genetic markers in herdwick sheep: no correlation with succeptibility or resistance to experimental scrapie.	genetic markers were studied in herdwick sheep, bred at compton, with special reference to genetically selected lines which differ in susceptibility or resistance to experimentally produced scrapie. there were no correlations between susceptibility to the disease and albumin, pre-albumin, esterase and haemoglobin phenotypes, and between reduced glutathione levels and alpha-mannosidase isoenzymes, the latter possibly representing a previously undescribed genetic marker in sheep.	1977	606000
rida in sheep. pathological and clinical aspects.		1978	645357
elimination of natural scrapie in sheep by sire genotype selection.		1979	759952
[kuru and creutzfeldt-jakob disease as examples of slow virus infections].		1976	765859
cellular sensitization in kuru, jakob-creutzfeldt disease and multiple sclerosis: with a note on the biohazards of slow infection work.	following intramuscular injection of kuru and jakob-creutzfeldt brain material into chimpanzees, circulating lymphocytes became sensitized to scrapie mouse brain (and spleen) to a greater degree than to normal tissue. this sensitization subsided after about a month, to be followed some 90 days later by a secondary peak attributed to establishment of changes in the nervous system. special sensitization to scrapie material occurs in kuru and jakob-creutzfeldt disease, but is not specific to them. ...	1975	766554
the pathology of a natural and experimental scrapie.		1976	782929
general introduction to some slow virus diseases.		1976	782930
biochemical and behavioural changes in scrapie.		1976	782931
extraneural competition between different scrapie agents leading to loss of infectivity.		1975	804143
the establishment of sheep flocks of predictable susceptibility to expirimental scrapie.	a selection experiment, based on a foundation stock of over 700 herdwick sheep and aimed at producing divergent populations of predictable high susceptibility or resistance to experimental scrapie was begun at this institute in 1961. twelve years later, flocks of presumed 100 per cent susceptibility to the cheviot-dervied scrapie agent ssbp-1 used throughout the experiment, and also manifesting a high incidence of the disease when challenged with other scrapie strains, are used in the compton sc ...	1975	804177
immunochemical studies on the storage and axonal transport of neurophysins in the hypothalamo-neurohypophyseal system.		1975	804289
host-pathogen interactions in scrapie.	there are many strains of the agent which causes scrapie and these can be used singly or given as mixed infections to investigate the ways in which agent and host control mechanisms interact during the pathogenesis of the disease. two genes in mice are described; one only affects the kinetics of the disease when extraneural injections are used, the other acts irrespective of the route of injection and it is suggested that it determines the structure of a multimeric agent-replication site, the nu ...	1975	807505