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At least 667 records · Page 37Linked to original sources
PubMed1992

Pyrimethamine resistant mutations in Plasmodium falciparum.

Three mutations in Plasmodium falciparum yielding increased resistance to pyrimethamine were obtained following treatment with chemical mutagens and selection in presence of pyrimethamine. From parasite clone TM4/8.2 a mutant, TM4/8.2/4.1, was produced which raised pyrimethamine resistance about 500 times and was found to involve an amino acid change in the DHFR-TS enzyme molecule from Ser108 to Asn108. A clone of another isolate, T9/94, yielded a mutant, T9/94/300.300, raising pyrimethamine resistance about 10 times and involving an amino acid change from Ile164 to Met164. However, another mutant from T9/94, T9/94/M1-1(b3), although it raised the pyrimethamine resistance 100 times, did not involve any changes in the coding sequence of the DHFR-TS gene, but resulted in the production of about twice as much DHFR-TS enzyme as the original clone T9/94. No amplification of the DHFR-TS gene was detected. It is concluded that changes in pyrimethamine resistance of malaria parasites may arise in at least 2 ways: (1) by structural changes in the DHFR domain of the DHFR-TS gene (as previously found by other workers); (2) by other changes, possibly affecting the expression of the DHFR-TS gene. The relative importance of these 2 mechanisms in causing resistance in wild populations of P. falciparum is discussed.

Animals↗
PubMed1985

Hemophilia A. Detection of molecular defects and of carriers by DNA analysis.

To understand the molecular basis of hemophilia A and to provide heterozygote detection and prenatal diagnosis by DNA analysis, we used cloned factor VIII:C DNA fragments to study 10 affected families. In four of these families, inhibitors of factor VIII:C had developed in affected persons. In one such family a deletion of approximately 80 kb within the factor VIII:C gene was identified. Carriers of the deletion were identified through detection of an abnormal DNA fragment located at the deletion end points. In another family a single nucleotide change in the coding region of the factor VIII:C gene produced a nonsense codon leading to premature termination of factor VIII:C synthesis. Carrier detection was performed in eight female members of this four-generation family. In a third family a small change in the size of a restriction-endonuclease fragment correlated with the presence of the mutant gene, and in the other seven families the molecular defect has not yet been identified. In addition, we used two common polymorphic sites in the factor VIII:C gene to differentiate the normal from the defective gene in four of six obligate female carriers from families with patients in whom inhibitors did not develop. Carrier detection was possible in other members of these families. These data suggest that DNA analysis of the factor VIII:C gene provides an accurate method of carrier detection and, potentially, of prenatal diagnosis in at least 50 per cent of the pedigrees affected by hemophilia A.

Chromosome Deletion↗
PubMed2000

Changes in tactile spatial discrimination and cutaneous coding properties by skin hydration in the elderly.

Neurosensory tactile functions were investigated in human subjects by two different and complementary experimental approaches. First, a conventional psychophysical method (two-point gap discrimination) was used to determine the tactile discrimination threshold by analyzing the subjects' ability to detect a gap of variable width between two contact points when a series of stimuli was applied to the skin. Using this method we confirmed the marked degradation of tactile spatial acuity with age and showed that skin discriminative function was partially restored after hydration of the skin with a moisturizer. The second approach consisted of a microneurographic recording of tactile afferent fibers in response to two types of mechanical stimuli applied reproducibly to the corresponding receptive fields. With this method, we found that the afferent messages were depressed following hydration of the skin surface. Thus, partial restoration of tactile spatial acuity after hydration appears to be due to both a softening of the stratum corneum permitting better localization of the stimulus and a weaker transfer of the stimulus toward the sensory receptors.

Adult↗
PubMed1997

A hospital pioneers reform of its state's procurement code.

In today's changing healthcare marketplace, hospitals across the US are rapidly moving toward developing integrated healthcare delivery networks. In addition, the emergence of managed care and the growing trend toward capitation have compelled hospitals to reduce costs in response to these changes. Moreover, this impetus to provide quality care at reduced cost has affected the purchasing behavior of many hospitals, forcing material managers to pursue innovative procurement methods. This article describes how the Medical University of South Carolina (MUSC) Medical Center, (Charleston, SC) obtained significant savings in purchasing as a result of pioneering legislative reforms in the procurement process.

Competitive Bidding↗
PubMed1984

[Changes in the content of matrix RNA coding tyrosine aminotransferase in the rat liver during hydrocortisone induction].

The effects of the glucocorticoid hydrocortisone on the synthesis of specific template RNA coding tyrosine aminotransferase (TAT) in rat liver during hormonal induction were studied. Using hybridization of complementary DNA (cDNA-TAT) with polysomal liver poly-A-mRNA, the content of specific mRNA-TAT in liver polysomes during and after hormonal induction, i. e. 4 and 16 hrs after hydrocortisone injection, respectively, was estimated. It was shown that 4 hrs after the hormone injection that mRNA-TAT content in liver polysomes is increased 3-4-fold, showing a return to the initial level after 16 hrs. Thus, transcription is the main link in the realization of glucocorticoid induction.

Animals↗
PubMed2001

Thrombomodulin promoter mutations, venous thrombosis, and varicose veins.

We analyzed the distal promoter region of the thrombomodulin (TM) gene (nucleotides -300 to -2052) in subjects from the Paris Thrombosis Study (PATHROS), a French case-control study of venous thrombosis, to identify polymorphisms that might modify TM gene expression. Eight novel mutations were found in the 40 DNA samples initially screened. Two of these mutations (-1748G/C and -1208/-1209 del TT) were frequent. One rare transition (-1166G/A) might have functional consequences owing to its position. These 3 mutations were screened for in the entire study population of 327 patients and 398 controls. None of the 3 was significantly associated with thrombosis. Interestingly, the -1208/-1209 TT deletion was associated with varicose veins in the patients. This mutation was in tight linkage disequilibrium with the +1418 C/T change in the coding sequence, a known polymorphism that predicts an Ala 455 Val substitution in the sixth epidermal growth factor-like TM module, a domain previously implicated in the proliferative functions of TM. This linkage suggests that the Ala 455 Val mutation may promote changes in these functions and thus be involved in varicose vein formation.

Adult↗
PubMed1995

Alterations in the structure of the EBV nuclear antigen, EBNA1, in epithelial cell tumours.

The EBV nuclear antigen, EBNA1, is the only viral protein consistently expressed in all virus-infected cells. It is required in trans for viral replication, maintenance of EBV extrachromosomal episomes, and transcriptional transactivation in latently-infected B-cells. It binds RNA suggestive of a regulatory role in post-transcriptional events and in transgenic mice, it is tumorigenic. In RNase protection studies relating to the EBV-associated tumour, nasopharyngeal carcinoma (NPC), we show that a C-terminal EBNA1 RNA probe from the prototype B95-8 marmoset strain can protect its own mRNA from enzymatic digestion, but does not fully protect EBNA1 mRNA from NPC cells. This finding is consistent with changes in the coding region for the antigen. We thus determined the sequences of EBNA1 genes derived from an NPC xenograft and numerous patient biopsies and identified a number of mutations in the gene in these human cells, relative to B95-8. Many of the nucleotide changes would lead to non-conservative amino acid alterations in apparently functionally significant regions of the protein. We show that although some of the mutations lie in regions designated as critical to DNA binding, they have negligible effect on this property of EBNA1. The basic regions in EBNA1 that may bind to RNA, at least in vitro, are exempt from mutation. Thus, unless the alterations are 'silent', which for such a critical viral function seems unlikely, they may relate to as yet unmapped viral activities, such as a role in tumorigenesis and the ability of EBNA1 to evade the cellular immune system, or be associated with the ability of the antigen to regulate gene transcription.

Amino Acid Sequence↗
PubMed1982

Structural diversity and differential light control of mRNAs coding for angiosperm glyceraldehyde-3-phosphate dehydrogenases.

Subunits A and B of chloroplast glyceraldehyde-3-phosphate dehydrogenase are synthesized as higher molecular weight precursors when polyadenylylated mRNA from angiosperm seedlings is translated in vitro by wheat germ ribosomes. The in vivo levels of mRNA coding for these precursors are strongly light dependent, and the increase in translational activity stimulated by continuous white light, relative to dark-grown seedlings, is at least 5- to 10-fold for the seven plant species investigated. As opposed to this, light does not seem to change mRNA levels coding for cytosolic glyceraldehyde-3-phosphate dehydrogenase, and the polypeptides synthesized in vitro have the same size as the authentic subunits. In addition, precursors of the chloroplast enzyme were identified for 12 different angiosperm species and compared with their respective subunits synthesized in vivo. The patterns of the in vitro and in vivo products correlate in several major characteristics. They both display a remarkable interspecific heterogeneity with respect to size and number of polypeptides. The peptide extensions of the enzyme precursors calculated from these data vary between 4,000 and 12,000 daltons and seem to fall into three major size classes. The present data demonstrate that chloroplast glyceraldehyde-3-phosphate dehydrogenase, like its cytosolic counterpart, is encoded in the nucleus. Yet, the two dehydrogenases are controlled differently at both the ontogenetic and phylogenetic levels. They follow separate biosynthetic pathways with respect to light regulation, post-translational processing, and transport and also exhibit different evolutionary rates. The fast evolutionary change observed for the chloroplast enzyme contrasts sharply with the conservative structure and sequence of the cytosolic enzyme.

Journal Article↗
PubMed2001

RP1 in Chinese: Eight novel variants and evidence that truncation of the extreme C-terminal does not cause retinitis pigmentosa.

Heterozygous truncating mutations in the RP1 gene cause approximately 7% of autosomal dominant retinitis pigmentosa (RP) cases. To examine the role of RP1 mutations in RP, we screened 101 unrelated Chinese RP patients (unselected for mode of inheritance) and 190 elderly normal control subjects for sequence changes in the coding exons for the 2156 amino acid RP1 protein. One patient had a mutation, thus RP1 mutations cause about 0.0% to 5.4% (95% confidence interval) of all RP among Chinese. The mutation was R677X, the most common found in Americans. Five other known sequence changes were found. In addition, nine novel sequence alterations were identified: 746G>A (R249H), 1437G>T (M479I), 2116G>C (G706R), 3024G>A (Q1008Q), 3188G>A (Q1063R), 5797C>T (R1933X), 6423A>G (I2141M), and the variants 6542C>T and 6676T>A, both in the 3' untranslated region. One control subject and three members of a non-RP family were heterozygous for R1933X, which is therefore likely to be a non-disease-causing variant. The most C-terminal truncation previously reported was due to Tyr1053 (1-bp del) and occurred in RP patients. Thus the presence of a normal level of at least part of RP1 between amino acids 1052 and 1933 appears necessary to prevent RP. Hum Mutat 17:436, 2001.

3' Untranslated Regions↗
PubMed1999

Finite-element morphometry of soft tissue morphology in subjects with untreated Class III malocclusions.

Soft tissue dynamics may contribute to maxillomandibular allometry (size-related changes in shape) associated with the development of Class III malocclusions. Lateral cephalographs of 124 prepubertal European American children were traced and 12 soft tissue landmarks were digitized. Resultant geometries were normalized, and Procrustes analysis established the statistical difference (p<0.001) between mean Class III and Class I configurations. Comparing the Class III configurations with normals for size-change, color-coded finite element analysis revealed a superoinferior gradient of positive allometry of the Class III facial nodal mesh. A conspicuous area of negative allometry (approximately 40%) was localized near soft subspinale, with a approximately 70% increase in size in the mental region. For shape-change, the Class III facial mesh was isotropic, except in the anisotropic circumoral regions. Conventional cephalometry revealed that about 50% of linear and 75% of angular parameters differed statistically (p<0.001). Soft tissue dynamics during early postnatal development may contribute to the development of Class III malocclusions.

Case-Control Studies↗
PubMed2001

Comparative sequences of two type 1 dengue virus strains possessing different growth characteristics in vitro.

The complete genome sequences of two dengue-1 virus strains having different growth characteristics (Mochizuki and A88) were compared with other published strains. The sequence analysis indicated several unique amino acid changes throughout the coding region of Mochizuki strain, mostly in envelope (E) protein. A unique amino acid, Ile-69 for Mochizuki strain at E protein resulted in the loss of an Asn-67-linked glycosylation site. A Thr substitution for Ala-114 at C protein and amino acid changes found in E, non-structural NS3, NS4a, and NS5 proteins were unique for A88 strain. These substitutions might be correlated to their different growth characteristics in vitro.

Amino Acid Sequence↗
PubMed1987

Nucleotide sequence of the insecticidal protein gene of Bacillus thuringiensis strain aizawai IPL7 and its high-level expression in Escherichia coli.

A DNA fragment carrying the insecticidal protein gene of Bacillus thuringiensis subsp. aizawai IPL7 was cloned from a 78-kb plasmid. The nucleotide sequence revealed that the cloned DNA fragment contained a 3465-bp protein-coding region with 156-bp 5'-flanking, and 168-bp 3'-flanking regions. The open reading frame encoded a 130,690 Da protein consisting of 1155 amino acid residues. Nucleotide sequence comparison of the aizawai gene with the published berliner 1715 gene showed only 8 nt changes in the coding regions. It was found that 72 bp of the 5'-flanking sequence of the cloned aizawai gene was responsible for constitutive expression of the 130-kDa protein gene in Escherichia coli. The expression was greatly enhanced by introducing the tac promoter upstream from the 72-bp 5'-flanking region of the aizawai gene. Under optimal conditions, the 130-kDa insecticidal protein amounted to 38% of the total cellular protein.

Amino Acid Sequence↗