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L G Goldfarb

Publications and source records attributed to L G Goldfarb.

86 records · Page 5Linked to original sources
PubMed1991

Clinical and molecular genetic study of a large German kindred with Gerstmann-Sträussler-Scheinker syndrome.

We have verified, by full open reading frame sequencing, the presence of an amino-acid-altering mutation in codon 102 of the scrapie amyloid protein gene in three affected members of a large and well-documented German family with experimentally transmitted Gerstmann-Sträussler-Scheinker syndrome. In addition, we identified the mutation by partial sequencing or DNA restriction enzyme analysis in three of 12 presently healthy family members with an affected parent, and none of 12 members without an affected parent. Thus, a total of six of 15 family members at risk for the disease (including the three established cases) had the same codon 102 mutation, a proportion consistent with the autosomal dominant inheritance pattern of disease expression. It is undetermined whether the mutation influences susceptibility to infection by an exogenous agent or is itself a proximate cause of disease.

Adult↗
PubMed1990

Detection of measles virus genomic sequences in SSPE brain tissue by the polymerase chain reaction.

The polymerase chain reaction (PCR) was modified to detect RNA genomic sequences by generating cDNA copies of these sequences as a preliminary step. Oligonucleotide primer pairs complementary to sequences in each of the five major structural protein genes of the measles virus (nucleocapsid protein, phosphoprotein, matrix protein, fusion protein, and hemagglutinin protein) were synthesized. PCR products were tentatively identified by visualization of bands of the appropriate size by ethidium bromide staining after gel electrophoresis, and identity was confirmed by subsequent restriction enzyme cleavage of the products at predetermined sites to yield fragments of predicted size. This method successfully amplified 400-500 base regions from each of these five genes in RNA extracts of wild measles virus cultured in Vero cells and in RNA extracted from most of the SSPE brain tissues tested, but not in RNA from any control brain tissues. Measles virus genome was detected in SSPE brain tissues stored frozen for as long as 27 years and formalin-fixed paraffin-embedded subacute sclerosing panencephalitis (SSPE) brain tissues as old as 9 years. This method provides a simple, rapid and highly sensitive means of detecting and identifying sequences of RNA genomes by PCR. The success of this method in detecting measles virus in SSPE brain tissue suggests that PCR is appropriate to investigate the possible presence of RNA viruses in other neurological disorders of unknown etiology.

Adolescent↗
PubMed1990

Creutzfeldt-Jakob disease and kuru patients lack a mutation consistently found in the Gerstmann-Sträussler-Scheinker syndrome.

We and others have recently reported that patients with the Gerstmann-Sträussler-Scheinker syndrome have a mutation at codon 102 of the gene coding for amyloid protein that accumulates in this disease. We report here that this mutation was not found in 5 familial and 27 sporadic cases of Creutzfeldt-Jakob disease or in 3 patients with kuru, so that although this mutation may be responsible for amyloidogenesis and transmissibility in Gerstmann-Sträussler-Scheinker syndrome, it cannot be the only cause of human spongiform encephalopathy.

Base Sequence↗
PubMed1989

Mutations in familial Creutzfeldt-Jakob disease and Gerstmann-Sträussler-Scheinker's syndrome.

A host protein encoded by the gene specifying the scrapie amyloid precursor affects pathogenesis of the transmissible spongiform encephalopathies: Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker's syndrome (GSS), and kuru in man, and scrapie in animals. We found a mutation in this gene of two patients with CJD from one family and a second mutation in the same gene in three patients with GSS from another family. The mutation in two related familial CJD patients changed glutamine in position 200 tolysine. This mutation was absent in other individuals including unrelated patients with familial CJD, sporadic CJD, and GSS. The other mutation in three GSS patients changed proline in position 102 to leucine, the same mutation described recently in some GSS families. We did not find it in six unaffected relatives of the GSS patients or in other individuals including sporadic and familial CJD patients. A rare insertion described earlier in one CJD family was also absent in all tested individuals.

Base Sequence↗
PubMed1989

Olivopontocerebellar atrophy in a large Iakut kinship in eastern Siberia.

One-hundred cases of olivopontocerebellar atrophy, type 1, were found and studied in the Iakut population of Eastern Siberia. The disease followed a slowly progressive course of cerebellar insufficiency caused by degeneration in the cerebellar cortex, nuclei pontis, and inferior oliva. The disorder shows an autosomal dominant pattern of inheritance with a lower penetrance in females. The disease spread from a small region in the Aldan valley 200 to 300 years ago.

Adolescent↗
PubMed1988

Seroprevalence of antibodies to HTLV-I in patients with chronic neurological disorders other than tropical spastic paraparesis.

Human T-lymphotropic virus type I (HTLV-I), the etiological agent of adult T-cell leukemia/lymphoma, also appears to be the cause of tropical spastic paraparesis, a chronic myelopathy reported in several different regions of the world. The prevalence of antibodies to HTLV-I in patients with chronic neurodegenerative disorders other than tropical spastic paraparesis and in patients with some muscle inflammatory disorders has been investigated. IgG antibodies to HTLV-I were measured in the sera and/or cerebrospinal fluid from 82 Guamanian patients with amyotrophic lateral sclerosis and parkinsonism-dementia, 164 Guamanian normal controls, 10 patients with kuru from the Eastern Highlands of Papua New Guinea, 4 patients with Viliuisk encephalomyelitis from the Iakut region of eastern Siberia, 45 Italian patients with multiple sclerosis, and 56 patients with polymyositis (49 from the United States and 7 from Jamaica). As determined by enzyme-linked immunosorbent assay, Western immunoblot, and gelatin particle agglutination techniques, serological evidence of HTLV-I infection was found in 1 patient with amyotrophic lateral sclerosis and 1 control subject from Guam, and in 1 patient from the United States and all 7 Jamaican patients with polymyositis. Except for the high seropositivity rate among the group of Jamaican patients with polymyositis, our data indicate that HTLV-I is an unlikely causative agent in the spectrum of the neurological diseases examined. The seropositivity of the 7 Jamaican patients with polymyositis requires further study.

Adult↗
PubMed1980

An epidemiological model of Crimean hemorrhagic fever.

A mathematical model of Crimean hemorrhagic fever (CHF) which satisfactorily describes the real epidemic process has been developed. Estimates of the intensity of infection and probability of disease have been obtained on the basis of the model. The probability of disease for subjects who had been infected was found to be a stable value characterizing the infection. In CHF, this value is 0.2153; in other words, the ratio of inapparent to clinically overt forms is approximately 5:1. By means of the model the causes of the lack of a stable immune portion among the human populations in CHF foci have been elucidated.

Adolescent↗
PubMedDate not supplied

Molecular genetic studies of Creutzfeldt-Jakob disease.

Genetic study of over 200 cases of Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker disease (GSS), fatal familial insomnia (FFI), and kuru have brought a reliable body of evidence that the familial forms of CJD and all known cases of GSS and FFI are linked to germline mutations in the coding region of the PRNP gene on chromosome 20, either point substitutions or expansion of the number of repeat units. No pathogenic mutations have so far been found in sporadic or infectious forms of CJD, although there are features of genetic predisposition in iatrogenic CJD and kuru. In FFI and familial CJD, clinically and pathologically distinct syndromes that are both linked to the 178Asp-->Asn substitution, phenotypic expression is dependent on a polymorphism at codon 129. Synthetic peptides homologous to several regions of PrP spontaneously form insoluble amyloid fibrils with unique morphological characteristics and polymerization tendencies. Peptides homologous to mutated regions of PrP exhibit enhanced fibrilogenic properties and, if mixed with the wild-type peptide, produce even more abundant and larger fibrous aggregates. A similar process in vivo may lead to amyloid accumulation and disease, and transmission of "baby fibrils" may induce disease in other hosts.

Amino Acid Sequence↗
PubMedDate not supplied

A novel mechanism of phenotypic heterogeneity demonstrated by the effect of a polymorphism on a pathogenic mutation in the PRNP (prion protein gene).

Fatal familial insomnia (FFI) is a subacute dementing illness originally described in 1986. The phenotypic characteristics of this disease include progressive untreatable insomnia, dysautonomia, endocrine and motor disorders, preferential hypometabolism in the thalamus as determined by PET scanning, and selective thalamic atrophy. These characteristics readily distinguish FFI from other previously described neurodegenerative conditions. Recently, FFI was shown to be linked to a mutation in the prion protein gene (PRNP) at codon 178, which results in the substitution of asparagine for aspartic acid. As such, FFI represents the most recent addition to the growing family of prion protein-related diseases. The mutation that results in FFI had previously been linked to a subtype of familial Creutzfeld-Jakob disease (178Asn CJD). The genotypic basis for the difference between FFI and 178AsnCJD lies in a polymorphism at codon 129 of the mutant prion protein gene: 129Met 178Asn results in FFI, 129Val 178Asn in CJD. The finding that the combination of a polymorphism and a single pathogenic mutation result in two distinct conditions represents a significant advance in our understanding of phenotypic variability.

Amino Acid Sequence↗