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C Shea

Publications and source records attributed to C Shea.

At least 55 records · Page 3Linked to original sources
PubMed1988

Stable variant-specific transcripts of the variant cell surface glycoprotein gene 1.8 expression site in Trypanosoma brucei.

The structure and transcriptional regulation of the 1.8 variant cell surface glycoprotein (VSG) gene expression site located on a 430-kilobase (kb) chromosome was examined in a 430-kb-chromosome-specific library. Using 32P-labeled nascent transcripts generated by nuclear run-on, we selected recombinant clones derived from the 430-kb chromosome which were coordinately activated with the 1.8 VSG gene. The results show that a repetitive region with a minimum size of 27 kb is coordinately activated with the 1.8 VSG gene. As with the 1.8 VSG gene, transcription is by RNA polymerases that are insensitive to the drug alpha-amanitin at concentrations up to 1 mg/ml. Transcription results in the generation of several stable variant-specific mRNAs. These mRNAs most likely belong to a family of repetitive expression-site-associated genes.

Animals↗
PubMed1987

VSG gene 118 is transcribed from a cotransposed pol I-like promoter.

To understand the control of differential variant cell surface glycoprotein (VSG) gene expression in T. brucei, we studied VSG gene and expression site transcription regulation. We show that the interchromosomal duplicative transposition of VSG gene 118, on an unusually large transposed segment, results in the transcriptional activation of a cotransposed RNA polymerase I-like (pol I) promoter, from which the VSG gene is transcribed. Transcription of VSG genes by pol I can therefore be regulated by DNA rearrangements that affect positional control of gene expression. A 5' cap is added in trans to the pol I-derived pre-mRNA, by addition of a pol II-derived 35 nucleotide mini-exon. A second gene (ESAG1) is located 25 kb upstream of the VSG 118 gene and is also transcribed. This expression site therefore contains at least two independently regulated genes. We discuss the putative importance of a nucleolar location for VSG gene and expression site transcription regulation.

Animals↗
PubMed1986

Variant surface glycoprotein gene expression site switches in Trypanosoma brucei.

In Trypanosoma brucei bloodstream forms, transcription of variant surface glycoprotein (VSG) genes occurs at only one of several possible expression sites at any given time. Activation and inactivation of some expression sites are correlated with recombinational events that alter their chromosomal position (Van der Ploeg, L. H. T., Cornelissen, A. W. C. A., Michels, P. A. M., and Borst, P. (1984) Cell 39, 213-221). We present evidence that a 430-kilobase pair (kb) chromosome, containing the 1.8 expression-linked copy, is taken up in a reciprocal recombination when the 1.8 gene is inactivated. As a result, the 430-kb chromosome is reduced in length either to 140 kb (in variant 118b') or to 350 kb (in variant MITat 1.2000) and the 1.8 expression-linked copy is moved to a larger chromosome in both cases. The subsequent activation of the telomeric 118 VSG gene in variant 118b', located on a 2000-kb chromosome, occurs without detectable recombinations while, for variant MITat 1.2000, still another expression site is activated. We discuss a model that explains the occurrence of these apparently random recombinational events at expression site switching and antigenic variation.

Animals↗
PubMed1986

Pel, the protein that permits lambda DNA penetration of Escherichia coli, is encoded by a gene in ptsM and is required for mannose utilization by the phosphotransferase system.

Mannose uptake and phosphorylation in Escherichia coli is catalyzed by the phosphoenolpyruvate:glycose phosphotransferase system (PTS). The mannose-specific complex of the PTS, designated IIMan, comprises lipid and two membrane proteins, II-AMan and II-BMan. The proteins are encoded by ptsM, located at approximately equal to 40 minutes on the E. coli chromosome. A different genetic marker, pel, maps with ptsM, and is required for lambda DNA penetration of the cytoplasmic membrane. Earlier studies suggested that both pel function and II-BMan are encoded by the same gene, while a different gene (also in ptsM) encodes II-AMan. In the present studies, a ptsM clone, pCS13, was isolated from an E. coli HindIII gene bank in pBR322 and restored both mannose termentation and pel+ function to ptsM mutants defective in II-BMan. Subclones of pCS13 show that two distinct genes, manY and manZ, encode the pel+ function and the II-BMan protein, respectively; each gene may have its own promoter; whereas the protein encoded by manY (Pel) alone seems sufficient for lambda sensitivity, all three gene products are required for mannose fermentation, transport of the mannose analogue 2-deoxyglucose, and phosphorylation of the latter by cytoplasmic membranes. Thus, Pel is required for function of the IIMan complex. The efficiency of the complex may depend on the ratio of Pel to IIMan.

Bacterial Proteins↗
PubMed1982

Solar urticaria: treatment with PUVA and mediator inhibitors.

Several therapeutic regimes for solar urticaria were evaluated. A short course of PUVA therapy produced a marked increase in the minimal dose of radiation required to produce urticaria in the six patients treated. This objective evidence of improvement was supported by the patients' reports of greatly increased tolerance to sun-exposure. Chlorpheniramine, an antihistamine, produced a slight increase in the minimal dose of radiation necessary to produce urticaria but its effectiveness was limited by side-effects. Indomethacin, an inhibitor of prostaglandin synthetase, produced no beneficial effect.

Adolescent↗
PubMed1981

Examination of Streptococcus mutans for immunoglobulin G Fc reactivity.

Representative strains of oral streptococci were tested for Fc immunoglobulin G (IgG) reactivity by two different techniques, agglutination of rabbit-IgG sensitized sheep erythrocytes and uptake of human and rabbit 125I-radiolabeled IgG. None of the S. mutans serotypes a through e reacted with the Fc region of either human or rabbit IgG. Additionally, other streptococci such as S. sanguis, S. salivarius, S. faecalis, and S. mitis failed to show appreciable Fc reactivity as assayed by these techniques. The group A, C, and G streptococci, previously shown to possess Fc reactivity, proved to be reactive in these experiments, as did a protein A-containing strain of Staphylococcus aureus.

Hemagglutination Tests↗
PubMed1980

Cross-reactivity of Streptococcus mutans antigens and human heart tissue.

Rocket and two-dimensional immunoelectrophoreses were used to demonstrate that antisera from rabbits immunized with Streptococcus mutans strain B13 cross-reacted with human heart tissue. Absorption of the anti-S. mutans serum with S. mutans whole cells removed all reactivity to heart tissue, but did not remove the reactivity of an added antibody marker to its corresponding antigen. The anti-S. mutans serum reacted most intensely with heart tissue antigen and to a lesser degree with skeletal muscle, but not with liver or kidney tissues. These results support the conclusion that antigens of S. mutans cross-react with mammalian heart tissue and, further, suggest that caution should be exercised in the formulation of a dental caries vaccine containing S. mutans antigens.

Antigens, Bacterial↗
PubMed1978

Peritoneal dialysis in rabbits. A study of transperitoneal theophylline flux and peritoneal permeability.

Since vasodilators can restore toward normal the decreased peritoneal clearances associated with vascular disease, the influence of aminophylline on peritoneal solute transport was studied in unanesthetized rabbits. Mean control creatinine clearance was 0.56 ml/kg/min and urea clearance 0.80 ml/kg/min. Neither intraperitoneal nor intravenous aminophylline increased peritoneal clearances, nor did the ratio creatinine clearance/urea clearance change from the control value, 0.70. Bidirectional flux of theophylline occurred at clearances of 0.70 ml/kg/min efflux and 0.64 ml/min influx. The removal rate of theophylline was 0.05% min, allowing therapeutic removal of excess aminophylline and warranting supplemental therapy during dialysis if therapeutic theophylline concentrations are required. As the intraperitoneal aminophylline was well tolerated, this route can be considered for therapeutic administration.

Aminophylline↗
PubMed1977

Isoproterenol enhancement of peritoneal permeability.

As peritoneal dialysis is inefficient enouth to be time-consuming and sometimes clinically ineffective, we have evaluated pharmacologic enhancement of peritoneal permeability. Peritoneal dialyses were performed in New Zealand white rabbits by instillation of 50 ml/Kg of isotonic dialysis solution of standard composition. Mean peritoneal clearance of creatinine was 0.60 ml/Kg/min and urea was 0.80 ml/Kg/min, each decreasing as intraperitoneal dwell was prolonged (by .011 ml/Kg/min or less). With 0.04 micrometer/Kg of isoproterenol administered intraperitoneally, clearances increased to 0.91 and 1.30 ml/Kg/min (p less than 0.01). When isoproterenol was added to the dialysis solution one hour or more before instillation, the increment in clearances was less. Instillation of dialysis solution 24 hours after addition of a higher dose of isoproterenol (0.2 micrometer/Kg) did not increase clearances above control. No effect of isoproterenol on bulk flow of water, associated with the osmotic effect of dextrose, was demonstrated. As peritoneal clearances increased, the ratio creatinine clearance: urea clearance did not decrease, consistent with increased peritoneal permeability as well as blood flow.

Animals↗
PubMed1977

Effect of intraperitoneal diuretics on solute transport during hypertonic dialysis.

Hypertonic periotoneal dialysis in New Zealand white rabbits results in increased dialyzate volume, but the sodium content of net ultrafiltrate is 109.5 MEq/l, less than extracellular fluid sodium concentration. With intraperitoneal furosemide, mean net ultrafilrate sodium concentration increased significantly to 121.2 mE1/l while ethacrynic acid had no such effect and both drugs affected dialyzate volume very slightly. Hypertonic peritoneal dialysis increased urea clearance significantly above isotonic dialysis and the addition of ethacrynic acid increased clearances further (P LESS THAN.02). Added furosemide decreased urea clearances suggesting that the effect on sodium transport is not an overall permeability change. During isotonic peritoneal dialysis, furosemide increased peritoneal permeability, i.e. urea and creatinine clearances, but a significantly higher urea clearance resulted from intraperitoneal ethacrynic acid. Furosemide influx clearance average 0.31 ml/kg/min, a mean of 27 percent of the urea clearance. The data suggest that furosemide may be useful to prevent the hypernatremia that may complicate hypertonic peritoneal dialysis, but is not as efficacious as other vasoactive drugs in enhancing peritoneal permeability.

Animals↗
PubMed1976

Photochemotherapy of vitiligo. Use of orally administered psoralens and a high-intensity long-wave ultraviolet light system.

A new light source that provides high-intensity ultraviolet light (UVA) (300 to 400 nm) to the entire body surface makes orally administered psoralen treatment of vitilligo with an artificial light practical. In the 26 patients studied, the degree of repigmentation with either trioxsalen (TMP) or methoxsalen (8-MOP) and high intensity UVA was at least as great as that with the same oral agents and sunlight. With artificial UVA and similar treatment conditions, the two psoralen derivatives were compared in the treatment of vitiligo; TMP stimulated repigmentation as well as 8-MOP and caused fewer side effects.

Administration, Oral↗
PubMedDate not supplied

Age-related increases in brain monoamine oxidase B in living healthy human subjects.

Several studies of human brain postmortem report that monoamine oxidase B (MAO B) increases with age and it has been proposed that this increase reflects age-associated increases in glial cells. We measured brain MAO B in a group of normal healthy human subjects (n = 21; age range 23-86; 9 females and 12 males; nonsmokers) using [11C]L-deprenyl-D2 and positron emission tomography. Brain glucose metabolism was also measured with 18FDG in 15 of the subjects. MAO B increased (p < 0.004) in all brain regions examined except the cingulate gyrus. In contrast, subjects showed the expected regional age-related decreases in blood flow and metabolism. In the 15 subjects in whom both MAO B and LCMRglu was measured, there was a trend (p < 0.03) toward an inverse association between brain glucose metabolism and MAO B activity in the frontal and parietal cortices. Although the age-related increase in brain MAO B in living subjects is consistent with postmortem reports, the degree of increase is generally lower.

Adult↗
PubMedDate not supplied

Inter-rater reliability of the diagnosis of vascular cognitive impairment at a memory clinic.

Consensus criteria for the diagnosis of vascular dementia (VaD) are gradually being replaced with data-based criteria. We report the inter-rater reliability of a new set of empirically-derived criteria for vascular cognitive impairment (VCI). Stratified sampling, with optimal allocation, was employed to randomly select 36 patients from the Queen Elizabeth II Health Science Centre's Memory Disability Clinic. Chart reviews were conducted independently by 4 physicians. Each physician classified the patients as having either: no cognitive impairment, VCI or Alzheimer's disease (AD). VCI was further classified both clinically (VCI without dementia, VaD or AD with a vascular component) and radiographically (infarcts, white matter changes, single strategic stroke). The intraclass correlation coefficient (ICC) for the diagnosis by physicians of VCI or otherwise was based on a repeated-measures analysis of variance with raters as the independent variable. A significant coefficient of reliability (average ICC = 0.88, 95% CI = 0.80-0.93) was obtained (H(o): rho </= 0.80, p = 0.03). Where differences in diagnosis occurred, the discrepancies most commonly resulted within the subtypes of VCI (9 cases) or between the diagnoses of AD and VCI (9 cases). Instances of diagnostic incongruity were typically due to the disagreement of a single rater (10 cases). This study demonstrates a high degree of reliability of criteria for VCI by physicians in a memory clinic, and can also be understood as an aspect of construct validation of those criteria. In the absence of a readily available biological marker for VCI, clinical criteria are necessary and can be reliably employed.

Activities of Daily Living↗