Cloning of the gene for ribosomal protein S13 from the fission yeast Schizosaccharomyces pombe.
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Amino Acid Sequence↗
Biomedical subjects
J Marks
Publications and source records attributed to J Marks.
Harm minimisation for drug misusers.
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Humans↗
Staphylococcal infection of hidradenitis excisions.
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Hidradenitis↗
The effect of interferon gamma on epidermal growth factor receptor expression in normal and malignant ovarian epithelial cells.
OBJECTIVE: We examined the effect of interferon gamma on proliferation and epidermal growth factor receptor expression in ovarian cancer cell lines and normal ovarian epithelial cells. STUDY DESIGN: The tritiated thymidine incorporation assay was used to assess the effect of interferon gamma on proliferation. Scatchard analysis of anti-epidermal growth factor receptor antibody binding, and Western blotting of immunoprecipitates was used to assess the effect of interferon gamma on epidermal growth factor receptor expression. RESULTS: Although interferon gamma elicited 30% to 40% decreases in proliferation, epidermal growth factor receptor expression was strikingly increased in all four ovarian cancer cell lines. Scatchard analysis indicated that this increase occurred primarily at the cell surface, but total cellular receptor levels also were increased. In contrast, interferon gamma treatment of normal ovarian epithelial cells affected neither proliferation nor epidermal growth factor receptor levels. CONCLUSION: Because the up-regulation of epidermal growth factor receptors by interferon gamma appears to be confined to malignant cells, interferon gamma may facilitate immunotherapy and imaging of ovarian cancers by means of immunoconjugates directed against the epidermal growth factor receptor.
Antibodies, Monoclonal↗
Genetic relationships among the apes and humans.
Epistemological difficulties and contradictory sets of molecular genetic data show that the question 'What is our closest living relative?' is surprisingly difficult to answer decisively. It is highly likely that we have not a single closest relative but, at the genus level, two equally close ones.
Animals↗
Popliteal-to-distal bypass for limb-threatening ischemia.
In a subset of patients requiring lower extremity revascularization, the popliteal artery may be used for inflow, thereby minimizing dissection and the length of vein required for bypass. This retrospective study was done to define the risks and benefits of arterial reconstruction in a population of patients having popliteal-to-distal bypass procedures. Between 1986 and 1990, 32 surgical procedures were performed on 29 patients. The patient's ages ranged from 46 to 86 years, with a mean age of 68 years. Twenty-four of 29 (83%) were men and 19 of the 29 (66%) had diabetes. Most patients had multiple indications for surgical intervention, and these included rest pain (54%), nonhealing ulcers (64%), and gangrene (29%). Arterial bypass with use of the popliteal artery for the proximal anastomosis was performed with in situ saphenous vein (50%), reversed saphenous vein (41%), and orthograde autologous vein (9%). Distal anastomoses were to the posterior tibial artery in 11 bypasses (33%), the peroneal artery in 10 (30%), the anterior tibial artery in two (6%), and the dorsal pedal artery in 10 (30%). Two deaths occurred in the perioperative period for an operative mortality rate of 6.9%. With use of life-table analysis, the cumulative graft patency rate was 97% at 1 year, 97% at 2 years, and 63.5% at 4 years. The overall cumulative limb salvage rate was 90.1% at 1 year, 90.1% at 2 years, and 78.8% at 4 years.(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗
Computational complexity of a problem in molecular structure prediction.
The computational task of protein structure prediction is believed to require exponential time, but previous arguments as to its intractability have taken into account only the size of a protein's conformational space. Such arguments do not rule out the possible existence of an algorithm, more selective than exhaustive search, that is efficient and exact. (An efficient algorithm is one that is guaranteed, for all possible inputs, to run in time bounded by a function polynomial in the problem size. An intractable problem is one for which no efficient algorithm exists.) Questions regarding the possible intractability of problems are often best answered using the theory of NP-completeness. In this treatment we show the NP-hardness of two typical mathematical statements of empirical potential energy function minimization of macromolecules. Unless all NP-complete problems can be solved efficiently, these results imply that a function minimization algorithm can be efficient for protein structure prediction only if it exploits protein-specific properties that prohibit the simple geometric constructions that we use in our proofs. Analysis of further mathematical statements of molecular structure prediction could constitute a systematic methodology for identifying sources of complexity in protein folding, and for guiding development of predictive algorithms.
Algorithms↗
Lymphomatoid papulosis: response to treatment with recombinant interferon alfa-2b.
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Adult↗
Cytoskeletal and DNA structure abnormalities result from bypass of requirement for the cdc10 start gene in the fission yeast Schizosaccharomyces pombe.
The cdc10 gene of the fission yeast S. pombe is required for traverse of the start control in late G1 and commitment to the mitotic cell cycle. To increase our understanding of the events which occur at start, a pseudoreversion analysis was undertaken to identify genes whose products may interact with cdc10 or bypass the requirement for it. A single gene, sct1+ (suppressor of cdc ten), has been identified, mutation of which suppresses all conditional alleles and a null allele of cdc10. Bypass of the requirement for cdc10+ function by sct1-1 mutations leads to pleiotropic defects, including microtubule, microfilament and nuclear structural abnormalities. Our data suggest that sct1 encodes a protein that is dependent upon cdc10+ either for its normal function or expression, or is a component of a checkpoint that monitors execution of p85cdc10 function.
Alleles↗
Genetic interactions in the control of septation in Schizosaccharomyces pombe.
We have used genetic and molecular techniques to investigate the interactions among genes required for the initiation and regulation of septum formation in Schizosaccharomyces pombe. Our data suggest that the products of the cdc7, cdc11, cdc14 and cdc16 genes interact. These activities may regulate the function of the cdc15 gene product. A model for the control of septation in fission yeast is presented.
Cell Division↗
Vertebrate p34cdc2 phosphorylation site mutants: effects upon cell cycle progression in the fission yeast Schizosaccharomyces pombe.
We have used the fission yeast Schizosaccharomyces pombe to analyse the effects of in vitro mutagenesis of the four known phosphorylation sites in the chicken p34(cdc2) protein, Thr 14, Tyr 15, Thr 161 and Ser 277, upon cell cycle progression. We have studied both the effect of overexpression of mutant proteins in a cdc2+ background and assayed their ability to rescue null and temperature-sensitive alleles of cdc2. Mutations of Thr 14 and Tyr 15 within the ATP binding domain of p34(cdc2) that mimic constitutive phosphorylation cause dominant negative cell cycle arrest when overexpressed. In contrast, some substitutions that simulate permanent dephosphorylation of the corresponding sites advance dephosphorylation of the corresponding sites advance mitosis. These data confirm the model that p34(cdc2) function is negatively regulated by phosphorylation of residues in the ATP binding site. Mutagenesis of the conserved residue Thr 161 functionally inactivates p34(cdc2), and our data suggest that both phosphorylation and dephosphorylation events at Thr 161 are required for progression through the cell cycle. Mutations at the fourth site of phosphorylation. Ser 277, lead to cold-sensitive cell cycle arrest, in minimal but not rich growth medium, suggesting that this site is involved in monitoring the nutritional status of the cell.
Amino Acid Sequence↗
What's old and new in molecular phylogenetics.
While it is fairly easy to devise a phylogenetic tree based on molecular data, it has proven difficult to tell how reliable any such tree is. Thus while the genetic inference that humans, chimpanzees, and gorillas cluster together is widely accepted, the genetic inference that the primary division among Old World human populations is between Asia and EurAfrica is not. A molecular phylogenetic inference linking humans and chimpanzees was proposed in the 1980s based on the technique of DNA hybridization. Despite several recent publications in primary and secondary source material, much confusion still exists surrounding the work. This paper tries to clarify issues that may still be confusing to physical anthropologists, and proposes criteria upon which to judge the robusticity of a phylogenetic inference based on DNA hybridization, in light of a recent published claim of replication. The claim of replication is considered critically. Interestingly, the original DNA hybridization data may actually show a chimp-gorilla link, in harmony with other phylogenetic results.
Animals↗
One gram of aspirin per day does not reduce risk of hospitalization for gallstone disease.
Data from 4524 patients in a randomized, controlled trial of aspirin were analyzed to determine if aspirin reduced the risk for hospitalization for gallstone disease. Aspirin at a dose of 1000 mg/day did not reduce the risk of hospitalization for gallstones. Hospitalization rates for gallstone disease were consistent with national rates, and the data confirmed previous associations of gallstone disease with age, elevated serum triglycerides, obesity, and female gender.
Adult↗
The adult alpha-globin locus of Old World monkeys: an abrupt breakdown of sequence similarity to human is defined by an Alu family repeat insertion site.
The haploid genomes of all known primates have two or more adult alpha-globin genes contained within tandemly arranged duplication units. Although the tandem duplication event generating these alpha-globin loci is believed to occur prior to the divergence of primates, a number of length polymorphisms exist within the loci among different primate species. In order to understand the molecular basis of these length polymorphisms, we have cloned and determined the nucleotide sequence of a major portion of the rhesus monkey adult alpha-globin locus. Sequence comparison to human suggests that the length difference between the adult alpha-globin loci of human and Old World monkey is the result of one or more DNA recombination processes, all of which appeared to be related to the transposition of Alu family repeats. First, the finding of a monomeric Alu family repeat at the junction between nonhomology block I and homology block Y of the alpha 2 gene-containing unit in rhesus macaque suggests that the dimeric Alu family repeat, Alu 3, at the orthologous position in human was generated by insertion of a monomeric Alu family repeat into the 3' end of another preexisting Alu family repeat. Second, two Alu family repeats, Alu 1 and Alu 2, exist in human at the 3' end of each of the two X homology blocks, respectively. However, this pair of paralogous Alu family repeats is absent at the corresponding positions in rhesus macaques. This raises interesting questions regarding the evolutionary origin of Alu 1 and Alu 2. Finally, DNA sequences immediately downstream from the insertion site of Alu 2 are completely different between human and rhesus macaque.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The placebo shrine.
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Clinical Trials as Topic↗
Siderophore presence in sputa of cystic fibrosis patients.
Sputum samples from the lungs of cystic fibrosis patients harboring Pseudomonas aeruginosa infections were collected and examined for the presence of the siderophore pyoverdine. Fluorescence quenching, due to the addition of ferric ion, as well as column and thin-layer chromatography results indicated that all samples contained the siderophore. Six samples furnished sufficient material after purification to allow us to obtain visible absorbance spectra. These spectra were characteristic of the ferrated analog of the P. aeruginosa pyoverdine, that is, ferripyoverdine, and in all cases they indicated a degree of ferration in excess of 50%. P. aeruginosa in the cystic fibrosis lung is thus iron stressed and responds by synthesizing pyoverdine, which subsequently binds ferric ion.
Adolescent↗
DNA hybridization as a guide to phylogeny: chemical and physical limits.
The technique of forming interspecific DNA heteroduplexes and estimating phylogenetic distances from the depression in their duplex melting temperature has several physical and chemical constraints. These constraints determine the maximum phylogenetic distance that may be estimated by this technique and the most appropriate method of analyzing that distance. Melting curves of self-renatured single copy primate DNAs reveal the presence of components absent from the renaturation products of exactly paired sequences. This observation, which confirms existing literature, challenges a fundamental assumption: that orthologous (i.e., corresponding) DNA sequences in the divergent species are being compared in DNA heteroduplex melting experiments. As a model system, the thermal stabilities of heteroduplexes formed between a human alpha-globin cDNA and four alpha-like globin genes isolated from chimpanzee are qualitatively compared. The results of this comparison show that the cross-hybrids of imperfectly matched gene duplicates from divergent species can contribute to the additional components that are present in renatured single copy DNAs. Single copy DNA, as usually defined, includes sequence duplicates that will obscure phylogenetic comparisons in a mass hybridization of genomes.
Animals↗