PubMed Health⌕ Search

Biomedical subjects

J R Sampson

Publications and source records attributed to J R Sampson.

At least 73 records · Page 4Linked to original sources
PubMed1990

Role of the tertiary nucleotides in the interaction of yeast phenylalanine tRNA with its cognate synthetase.

In vitro transcription by T7 RNA polymerase was used to prepare 32 different mutations in the 21 nucleotides that participate in the 9 tertiary base pairs or triples of yeast tRNAPhe. The mutations were designed either to disrupt the tertiary interaction or to change the sequence without disrupting the structure by transplanting tertiary interactions present in other tRNAs. Steady-state aminoacylation kinetics with purified yeast phenylalanyl synthetase revealed little change in reaction rate as long as a tertiary interaction was maintained. This suggests that the tertiary nucleotides only contribute to the folding of tRNAPhe and do not participate directly in sequence-specific interaction with the synthetase.

Amino Acyl-tRNA Synthetases↗
PubMed1990

Genetic heterogeneity in tuberous sclerosis.

Tuberous sclerosis (TSC) is an autosomal dominant disorder characterized by widespread hamartosis. Preliminary evidence of linkage between the TSC locus and markers on chromosome 9q34 was established, but subsequently disputed. More recently, a putative TSC locus on chromosome 11 has been suggested and genetic heterogeneity seems likely. Here we describe an approach combining multipoint linkage analysis and heterogeneity tests that has enabled us to obtain significant evidence for locus heterogeneity after studying a relatively small number of families. Our results support a model with two different loci independently causing the disease. One locus (TSC1) maps in the vicinity of the Abelson oncogene at 9q34 and a second locus (TSC2) maps in the region of the anonymous DNA marker Lam L7 and the dopamine D2 receptor gene at 11q23.

Chromosome Mapping↗
PubMed1990

Effect of erythropoietin therapy on diet and dialysis clearances in hemodialysis patients.

Treatment of renal anemia with recombinant human erythropoietin in chronic hemodialysis patients has been reported to lead to increased appetite, and in several studies, to an increase in predialysis serum urea, potassium and creatinine values. We recorded dietary intake, and dialysis clearances for creatinine, urea and uric acid in a group of 12 anemic hemodialysis patients treated with recombinant erythropoietin (epoetin beta). A gradual increase was noted in dietary intake of calories, carbohydrate and sodium during the study period, attaining statistical significance after 10-12 months of therapy. A trend toward increased dietary intake of protein, lipid and potassium was observed, but the differences did not achieve statistical significance. Although a trend toward decreased dialysis clearance at higher hematocrits was found for creatinine clearances did not change significantly for any of the solutes examined, and linear regression analysis did not demonstrate a strong relationship between dialyzer clearance and hematocrit values within the range observed in this study.

Adult↗
PubMed1989

Structure of an unmodified tRNA molecule.

We have used NMR to study the structure of the yeast tRNA(Phe) sequence which was synthesized by using T7 RNA polymerase. Many resonances in the imino 1H- spectrum of the transcript have been assigned, including those of several tertiary interactions. When the Mg2+ concentration is high, the transcript appears to fold normally, and the spectral features of the transcript resemble those of tRNA(Phe). The transcript has been shown to be aminoacylated with kinetics similar to the modified tRNA(Phe) [Sampson, J. R., & Uhlenbeck, O. C. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 1033-1037], suggesting that the structure of the two molecules must be similar. In the absence of Mg2+ or at [tRNA]:[Mg2+] ratios less than 0.2, the transcript does not adopt the native structure, as shown by both chemical shifts and NOE patterns. In these low Mg2+ conditions, a second GU base pair is found, suggesting a structural rearrangement of the transcript. NMR data indicate that the structure of a mutant having G20 changed to U20 is nearly identical with that of the normal sequence, suggesting that the low aminoacylation activity of this variant is not due to a substantially different conformation.

Base Composition↗
PubMed1989

Nucleotides in yeast tRNAPhe required for the specific recognition by its cognate synthetase.

An analysis of the aminoacylation kinetics of unmodified yeast tRNAPhe mutants revealed that five single-stranded nucleotides are important for its recognition by yeast phenylalanyl-tRNA synthetase, provided they were positioned correctly in a properly folded tRNA structure. When four other tRNAs were changed to have these five nucleotides, they became near-normal substrates for the enzyme.

Amino Acyl-tRNA Synthetases↗
PubMed1989

Oliver McFarlane syndrome: a 25-year follow-up.

We describe findings in a 29-year-old woman with Oliver McFarlane syndrome after 25 years of follow-up, and we review findings in six other reported cases. Pigmentary retinal degeneration, trichomegaly, prenatal onset growth failure, anterior pituitary deficiencies, and peripheral neuropathy characterize the condition.

Abnormalities, Multiple↗
PubMed1989

Dermatoses in five related female carriers of X-linked chronic granulomatous disease.

Eight female members of a family with X-linked chronic granulomatous disease were identified. Five were shown to be carriers of the disease gene. Each of these female carriers of the gene had a history of skin eruptions. The identification of the carrier state is important as genetic counselling should be offered and the prenatal diagnosis of this disorder is possible.

Adult↗
PubMed1989

Genetic aspects of tuberous sclerosis in the west of Scotland.

Complete ascertainment of tuberous sclerosis was attempted in the west of Scotland (population 2,763,000). A total of 101 patients was identified, giving an overall minimum prevalence of 1 in 27,000, but for children under 10 years of age the minimum prevalence was 1 in 12,000. Both parents of 84 of the ascertained cases were assessed for signs of tuberous sclerosis. In 51 pairs of parents no evidence of the condition was seen, indicating that up to 60% of the cases were new mutations. The mutation rate was estimated at 2.5 X 10(-5) mutations per gene per generation. Analysis of parental ages for the new mutations did not show a significant age effect. Thirty-five patients occurred in 13 families containing other affected subjects. The pattern of inheritance was consistent with an autosomal dominant trait in these families. In one sibship, non-penetrance or gonadal mosaicism resulted in affected sibs with normal parents. Of two further sibships where non-penetrance was suspected, one was shown to represent a single new mutation in monozygotic twins and the other to involve non-paternity.

Adult↗
PubMed1989

Evidence for genetic heterogeneity in tuberous sclerosis.

The question of genetic heterogeneity in tuberous sclerosis (TSC) was addressed by genetic linkage studies in eight affected families using nine polymorphic markers (EFD126.3, MCT136, ABO, ABL, AK1, and MCOA12 from distal 9q, and PBGD, MCT128.1, and 1CJ52.208M from distal 11q). The data as a whole supported a TSC locus on distal 9q, the peak lod score on multipoint analysis being 3.77 at 6 cM proximal to the Abelson oncogene locus (ABL). However, analysis of two point lod scores using the HOMOG programs showed significant evidence for genetic heterogeneity (p = 0.01), linkage to ABL being unlikely in one family. After exclusion of the unlinked family, multipoint analysis gave a peak lod score of 6.1 in the vicinity of ABL. The family unlinked to ABL showed no recombinants with two chromosome 11 probes, but was too small to provide significant evidence for linkage. Genetic heterogeneity in TSC will complicate efforts to clone the causative genes and severely limit the use of linked probes for carrier detection and prenatal diagnosis.

Chromosome Mapping↗
PubMed1988

Biochemical and physical characterization of an unmodified yeast phenylalanine transfer RNA transcribed in vitro.

A recombinant plasmid was constructed with six synthetic DNA oligomers such that the DNA sequence corresponding to yeast tRNA(Phe) is flanked by a T7 promoter and a BstNI restriction site. Runoff transcription of the BstNI-digested plasmid with T7 RNA polymerase gives an unmodified tRNA of the expected sequence having correct 5' and 3' termini. This tRNA(Phe) transcript can be specifically aminoacylated by yeast phenylalanyl-tRNA synthetase and has a Km only 4-fold higher than that of the native yeast tRNA(Phe). The Km is independent of Mg2+ concentration, whereas the Vmax is very dependent on Mg2+ concentration. Comparison of the melting profiles of the native and the unmodified tRNA(Phe) at different Mg2+ concentrations suggests that the unmodified tRNA(Phe) has a less stable tertiary structure. Using one additional DNA oligomer, a mutant plasmid was constructed having a guanosine to thymidine change at position 20 in the tRNA gene. A decrease in Vmax/Km by a factor of 14 for aminoacylation of the mutant tRNA(Phe) transcript is observed.

Base Sequence↗
PubMed1987

A universe for molecular modeling of self-replication.

An abstract two-dimensional universe is presented, in which self-replication can be modeled and studied by computer simulation. Two types of permanent elements (atoms) occupy squares of the universe. Atoms sharing a common square form a particle, with properties determined by its component atoms. Atoms, particles, and complexes of particles move and collide according to rules like those of classical mechanics. At a higher level of organization, the string of atoms in a particle is viewed as a program, whose execution can affect the space around the particle in ways similar to the operation of enzymes. Two systems that exhibit self-replication when embedded in the universe are demonstrated. The first is very simple showing elementary self-replication activity. The second is relatively elaborate and intended to show "on paper" how a collection of particle complexes could behave in a manner resembling mitosis in a simple cell.

Biological Evolution↗
PubMed1977

A random walk model of cellular kinetics.

The sorting out of biological cell mixtures into clusters of one cell type is modelled as a consequence of random cell and cluster motion, during which cells of like type cohere upon collision. After a description of the model and its motility rules, the results of several computer simulation studies are analysed and compared with both laboratory data and certain theoretical predictions. The model is found to be more biologically realistic than previous models with similar results. Suggestions for further reserach are discussed. An Appendix contains details about the data structures and algorithms employed in the simulation.

Cell Adhesion↗