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F Cathala

Publications and source records attributed to F Cathala.

At least 19 recordsLinked to original sources
PubMed1999

[Brief history of transmissible spongiform encephalopathies].

Transmissible spongiform encephalopathies have a long and still unfinished history replete with spectacular discoveries and equally spectacular failures. The story begins in the 18th century with the first descriptions of scrapie, a naturally contagious disease of sheep that was not experimentally proven to be a transmissible infection until 1936. This discovery permitted veterinarian investigators to begin to explore aspects of pathogenesis and the nature of the infectious agent. The additional discovery, in the 1960's, that scrapie was similar to the human diseases kuru and Creutzfeldt-Jakob vastly widened what had been a comparatively restricted field of research, and led to rapid advances in molecular characterization of the disease agents, culminating in the proposal that they are self-replicating abnormally configured host proteins, or "prions". Despite these advances, we have seen in recent years 3 potentially preventable outbreaks of disease: iatrogenic Creutzfeldt-Jakob disease due to contaminated pituitary hormone extracts and dura mater grafts, and a new variant of the disease (Will-Ironside syndrome) linked to consumption of beef contaminated by the agent of bovine spongiform encephalopathy, underscoring the disparity between fundamental knowledge and its practical application.

Disease Outbreaks↗
PubMed1999

Natural and experimental oral infection of nonhuman primates by bovine spongiform encephalopathy agents.

Experimental lemurs either were infected orally with the agent of bovine spongiform encephalopathy (BSE) or were maintained as uninfected control animals. Immunohistochemical examination for proteinase-resistant protein (prion protein or PrP) was performed on tissues from two infected but still asymptomatic lemurs, killed 5 months after infection, and from three uninfected control lemurs. Control tissues showed no staining, whereas PrP was detected in the infected animals in tonsil, gastrointestinal tract and associated lymphatic tissues, and spleen. In addition, PrP was detected in ventral and dorsal roots of the cervical spinal cord, and within the spinal cord PrP could be traced in nerve tracts as far as the cerebral cortex. Similar patterns of PrP immunoreactivity were seen in two symptomatic and 18 apparently healthy lemurs in three different French primate centers, all of which had been fed diets supplemented with a beef protein product manufactured by a British company that has since ceased to include beef in its veterinary nutritional products. This study of BSE-infected lemurs early in their incubation period extends previous pathogenesis studies of the distribution of infectivity and PrP in natural and experimental scrapie. The similarity of neuropathology and PrP immunostaining patterns in experimentally infected animals to those observed in both symptomatic and asymptomatic animals in primate centers suggests that BSE contamination of zoo animals may have been more widespread than is generally appreciated.

Animals↗
PubMed1995

[A funny story].

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Animals↗
PubMed1995

[Human spongiform encephalopathies].

Clinical descriptions of Creutzfeldt-Jakob disease by the classical authors are compared with 209 transmitted cases at NIH between 1968-1992. Clinical comparison between Kuru, Gertsmann-Sträussler-Sheinker Syndrome and Creutzfeldt-Jakob disease. Fatal Familial Insomnia is included into the latter. Familial forms: new acquisitions.

Adolescent↗
PubMed1992

Creutzfeldt-Jakob disease cosegregates with the codon 178Asn PRNP mutation in families of European origin.

We recently discovered an amino acid-altering heterozygous mutation in codon 178 of the PRNP amyloid precursor gene in patients with familial Creutzfeldt-Jakob disease. This mutation is now shown to be associated with the occurrence of disease in 7 unrelated families of Western European origin, among which a total of 65 members are known to have died from Creutzfeldt-Jakob disease. The mutation was detected in each of 17 tested patients, including at least 1 affected member of each family, and in 16 of 36 of their first-degree relatives, but not in affected families with other mutations, patients with the nonfamilial form of the disease, or 83 healthy control individuals. Linkage analysis in two informative families yielded a lod score of 5.30, which, because no recombinants were found, strongly suggests that codon 178Asn is the actual disease mutation.

Adult↗
PubMed1992

Phenotypic characteristics of familial Creutzfeldt-Jakob disease associated with the codon 178Asn PRNP mutation.

A group of 43 patients from seven families affected by Creutzfeldt-Jakob disease (CJD) with the codon 178Asn mutation of the PRNP amyloid precursor gene is compared to a group of 211 patients with the sporadic form of the disease. As a group, the patients with the codon 178Asn mutation had an earlier age at onset of illness (almost always presenting as an insidious loss of memory), a longer duration of illness, and an absence of periodic electroencephalographic activity. Transmission of disease to primates was accomplished using brain tissue homogenates from 6 of 10 patients, resulting in significantly shorter incubation periods than those due to sporadic CJD inocula. These findings are interpreted and discussed in terms of possible differences in the temporospatial evolution of damage to the brain, and of accelerated induction of polymerized amyloid protein by its mutationally altered template precursor.

Age Factors↗
PubMed1992

An insert mutation in the chromosome 20 amyloid precursor gene in a Gerstmann-Sträussler-Scheinker family.

We report the finding of an insert mutation in the chromosome 20 amyloid precursor gene in a family with neuropathologically-verified, experimentally-transmitted Gerstmann-Sträussler-Scheinker syndrome (GSS). The insert consisted of 8 extra copies of a repeating octapeptide coding sequence in the region between codons 51 and 91; it was identified in the proband and a presently unaffected at-risk niece by full sequencing of the open reading frame, and was visualized electrophoretically in the proband and 6 of 12 at-risk relatives. Although affected members in this French-Breton family have shown a variety of clinical profiles, including durations of illness that ranged from 3 months to 13 years, all autopsied cases (including the patient with the shortest illness) have had the distinctive multicentric amyloid plaques that define GSS as a nosologic entity.

Adult↗
PubMed1991

The molecular genetics of familial Creutzfeldt-Jakob disease in France.

Five French families with Creutzfeldt-Jakob disease (CJD) were found to have either of 2 different point mutations (at codons 178 and 200) in the amyloid precursor gene (PRNP) on chromosome 20. The ancestry of these and other CJD families outside of France suggests that the codon 178 mutation had a northern European origin, while the codon 200 mutation originated in central Europe and the Mediterranean basin. Evidence is presented that the mutations either cause or predispose to familial forms of CJD, and also influence their phenotypic expression, although considerable clinical and neuropathological heterogeneity may occur between and even within families having the same mutation. Experimental transmission of disease was successful in 4 of 5 inoculated cases, comparable to the transmission rate in sporadic CJD.

Amyloid beta-Protein Precursor↗
PubMed1991

[Analysis of the PrP gene in a Tunisian family with Creutzfeldt-Jakob disease].

Results of PrP gene analysis in 5 of 9 members from a Jewish Tunisian family with Creutzfeldt-Jakob disease (CJD) showed a mutation at codon 200 involving substitution of lysine (Lys200) for glutamic acid (Glu200). This observation suggests that Lys200 allele probably tracks with CJD in this family and supports the possible genetic basis of the disease in the Mediterranean cluster. A second PrP variant not associated with Lys200 allele involving a short deletion in the coding sequence has also been found in only one subject.

Creutzfeldt-Jakob Syndrome↗
PubMed1989

The question of clustering of Creutzfeldt-Jakob disease.

Clustering of Creutzfeldt-Jakob disease has been reported in several countries. The authors review these reports, and they describe their statistical analysis of clustering among 329 cases that died in France during 1968-1982. Paris was found to have a much higher case rate than the rest of France, while some large areas in the north and west had remarkably few cases relative to their populations. No rural clusters were identified. A number of explanations for regional variations in case rates are possible, including population characteristics and case finding artifacts. Based on their results and those of other studies, the authors conclude that the strongest evidence for clustering of Creutzfeldt-Jakob disease is familial and ethnic, rather than geographic.

Africa, Northern↗
PubMed1988

Sheep major histocompatibility (OLA) complex: linkage between a scrapie susceptibility/resistance locus and the OLA complex in Ile-de-France sheep progenies.

As seen on their family trees, Ile-de-France sheep with scrapie show genetic susceptibility to this disease, which is transmitted via scrs, an autosomal recessive gene. Scrapie occurred in homozygous recessive sheep, whereas the presence of the dominant resistance allele Scrr sufficed to prevent this disease in heterozygous animals. This hypothesis, previously proposed by Parry (1962), was tested in a study involving 133 crossings of sheep of different genotypes, and verified in the observed progenies. In a contaminated environment, susceptibility to the disease seemed to be transmitted by the scrs gene, whose frequency was increasing and varied in different progenies: the gene was propagated by inbreeding combined with selection; scrapie did not appear in the progeny of a homozygous resistant ram with the Scrr/Scrr genotype. On the family trees, linkage between the Scr locus and the OLA-A and -B loci is clearly visible; it often allowed the transmission of resistance or susceptibility haplotypes to be detected by OLA typing and followed from one generation to the next. The Scrr, OLA-A4, B6 haplotype was not found in any diseased sheep born before 1979, but was propagated by healthy sheep. During and after 1979, several recombinations of this haplotype were observed, giving a recombined haplotype with reciprocal linkage (scrs, OLA-A4, B6), disseminated by one sire in particular. The rate of recombination of Scr and OLA loci is estimated to be between 11 and 16%. The possibility of early selection against the disease without loss of qualities desired by the breeder is discussed.

Animals↗
PubMed1987

Impairment of the cortical and thalamic electrical activity in scrapie-infected rats.

Cortical and thalamic EEG and somatosensory evoked potential (SEP) induced by stimulation of the somesthetic radiations were studied in scrapie-infected rats. Animals were inoculated intracerebrally with a rat-adapted strain (originating in the C506 M3 mouse scrapie strain). EEG and SEP were recorded from 9 to 17 months after inoculation (ti). Abnormalities (paroxysmal bursts, isolated spikes) first occurred in the cortex (parietal areas) and later in the thalamus, where they were usually less marked. Latencies of the postsynaptic components of the SEP increased at ti + 9 months. This effect became progressively more pronounced and at ti + 15 months, latencies of presynaptic components were also delayed. Nevertheless, marked alteration of the SEP occurred only at the terminal stage of the disease. These findings show that the scrapie-induced disturbances affect more especially the cortex. Decrease of inhibitory processes as well as electronic coupling between cells, resulting from the virus-induced membrane fusion, could produce paroxysmal activity of EEG and SEP impairments.

Animals↗
PubMed1987

The epidemiology of Creutzfeldt-Jakob disease: conclusion of a 15-year investigation in France and review of the world literature.

During the 15-year period 1968-1982, a total of 329 patients dying of Creutzfeldt-Jakob disease (CJD) were identified in continental France. Annual mortality rates stabilized at 0.5 to 0.6 cases per million (1.1 to 1.2 cases per million in Paris). Six percent of cases were familial. Although the frequency of CJD was related to population density, no contacts could be established among the great majority of patients. No association with socioeconomic factors, preceding trauma or surgery (excepting one iatrogenic neurosurgical case), or exposure to animal sources of infection was identified. Evidence from this and other epidemiologic studies suggests that CJD is a minimally contagious disease that may be principally acquired in early life from presymptomatic patients, asymptomatic carriers, or chance contamination by environmental sources. It is possible that CJD could also occur sporadically as a noncontagious disease by a mechanism akin to oncogenes in carcinogenesis.

Adolescent↗
PubMed1986

Spread of scrapie agent to the central nervous system: study of a rat model.

Invasion of scrapie agent into the central nervous system (CNS) was studied in rats following intracerebral and peripheral inoculation, the latter by injection into intact or transected sciatic nerve. Comparison of sleep-wakefulness alterations, neuropathological features, and time lag of electroencephalographic and clinical signs in the 3 groups suggests that hematogenous spread of infection to the CNS may predominate over neural transport, and that peripheral inoculation may closely approximate natural infection.

Animals↗
PubMed1986

Changes in the serotonergic, noradrenergic and dopaminergic levels in the brain of scrapie-infected rats.

Levels of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylethyleneglycol (DHPG) were determined by high-performance liquid chromatography in different brain areas of scrapie-infected rats, 8.5 months after intracerebral inoculation of a rat-adapted strain from mice brain (C 506). At this time, rats developed early clinical signs of the disease. Scrapie-infected rats showed a reduction in the levels of 5-HT and 5-HIAA (frontal cortex, hippocampus, mesolimbic structure). Concentrations of DHPG decreased in the frontal and parietal cortices but remained unchanged in the hippocampus. DOPAC levels decreased in the striatum but not in the mesolimbic structure. These results confirm that the serotonergic, noradrenergic and dopaminergic systems are altered in the brain of scrapie-infected rats. They can partly account for clinical signs of scrapie and are in agreement with the scarce data provided by the postmortem analysis of Creutzfeldt-Jakob disease brains.

3,4-Dihydroxyphenylacetic Acid↗