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Biomedical subjects

C Doyle

Publications and source records attributed to C Doyle.

At least 109 records · Page 6Linked to original sources
PubMed1988

Transport handicap--its causes, its scale and its effect.

It has become clear during all stages of our research that transport plays a vital part in enabling disabled people to live independent lives and to be a full part of the community in which they live. All Change, a consumers study of public transport handicap in Greater London, published in 1986, sought to gather information about the scale, causes, and extent of transport handicap in the Greater London area. The findings are based on interviews from people who define themselves as transport handicapped.

Automobiles↗
PubMed1987

Sequence-specific interactions of nuclear factors with conserved sequences of human class II major histocompatibility complex genes.

All class II major histocompatibility complex genes contain two highly conserved sequences, termed X and Y, within the promoter regions(s), which may have a role in regulation of expression. To study trans-acting factors that interact with these sequences, sequence-specific DNA binding activity has been examined by the gel electrophoresis retardation assay using the HLA-DQ2 beta gene 5' flanking DNA and nuclear extracts derived from various cell types. Several specific protein-binding activities were found using a 45-base-pair (bp) HinfI/Sau96I (-142 to -98 bp) and a 38-bp Sau96I/Sau96I (-97 to -60 bp) fragment, which include conserved sequence X (-113 to -100 bp) and conserved sequence Y (-80 to -71 bp), respectively. Competition experiments, methylation interference analysis, and DNase I foot-printing demonstrated that distinct proteins in a nuclear extract of Raji cells (a human B lymphoma line) bind to sequence X, to sequence Y, and to DNA 5' of the X sequence (termed sequence W). The factor binding site in the W sequence is also found to be conserved among beta-chain genes and is suggested to be a gamma-interferon control region.

B-Lymphocytes↗
PubMed1986

Clinical experience with ciprofloxacin in the USA.

This interim analysis of the efficacy and safety of ciprofloxacin is based on case reports of 1241 adult patients treated primarily in the USA; 1026 were suitable for analysis of drug efficacy. The daily dose ranged from 500 to 1500 mg, the unit dose being given every 12 h. Duration of treatment ranged from 5 to 211 days (mean 12.6 days). In 1046 cases of infection the site was the urinary tract (514), skin structures (218), respiratory tract (215), blood (43), bone (27), abdomen (13), gastrointestinal tract (13) and pelvis (3). Organisms responsible for infection were Escherichia coli (282), Pseudomonas aeruginosa (238), Staphylococcus spp. (149), Streptococcus spp. (107), Klebsiella spp. (105), Proteus spp. (97), Haemophilus spp. (71), Enterobacter spp. (58), Salmonella spp. (44), Citrobacter spp. (27), and Serratia spp. (22). Signs and symptoms of infection resolved in 84% of all cases; 12.6% improved and 3.4% failed to improve. Pathogens were eradicated in 91% of urinary tract infections and in 87% of all other cases of infection combined; superinfections occurred in 5.3% of all patients. At the four-week follow-up 83% of patients with urinary tract infection still had sterile urine. Adverse reactions during therapy were considered probably or possibly drug-related in 166 patients. Nausea (37), diarrhea (25), vomiting (15), nervousness (28), and rash (9) were the most frequent; in only 2% of cases was it necessary to discontinue the drug. Results of ophthalmologic studies were generally unremarkable. Occasional elevations of SGOT and SGPT, and rare elevations of NPN related to ciprofloxacin therapy were seen.

Administration, Oral↗
PubMed1986

Evaluation of acute bioassays for assessing toxicity of polychlorinated biphenyl-contaminated soils.

Proposed State of California regulations use fish toxicity information as one criterion in municipal or industrial waste hazard evaluation. Static 96-hr bioassays were performed using fathead minnows (Pimephales promelas), blacksmith (Chromis punctipinnis), and glass shrimp (Palaemonetes kadiakensis) exposed to soil experimentally contaminated with up to 500 ppm polychlorinated biphenyl (PCB) capacitor fluid added at a concentration of 500 mg liter-1. Other bioassays were conducted with a 6-day mixing period prior to the bioassay or with acetone added to solubilize the PCBs. No mortality attributable to PCB toxicity was observed in definitive bioassays using the two fish and one invertebrate species. PCB levels leached from soil containing 500 ppm Aroclor 1242 ranged from less than 0.6 to 3.4 ppb in freshwater tests to 3.5 ppb in seawater bioassays. Using these data as the basis for waste classification, soils contaminated with up to 500 ppb PCBs during capacitor spills would be designated nonhazardous. PCBs are known to be environmentally persistent and to bioaccumulate. Acute toxicity tests, therefore, do not adequately evaluate the general toxicity of PCB-contaminated soils. Hazardous waste regulations for hydrophobic compounds such as PCBs should instead be based upon chronic toxicity data and should also consider bioaccumulation potential.

Animals↗
PubMed1986

Heterologous transmembrane and cytoplasmic domains direct functional chimeric influenza virus hemagglutinins into the endocytic pathway.

Chimeric genes were created by fusing DNA sequences encoding the ectodomain of the influenza virus hemagglutinin (HA) to DNA coding for the transmembrane and cytoplasmic domains of either the G glycoprotein of vesicular stomatitis virus or the gC glycoprotein of Herpes simplex virus 1. CV-1 cells infected with SV40 vectors carrying the recombinant genes expressed large amounts of the chimeric proteins, HAG or HAgC on their surfaces. Although the ectodomains of HAG and HAgC differed in their immunological properties from that of HA, the chimeras displayed the biological functions characteristic of the wild-type protein. Both HAG and HAgC bound erythrocytes as efficiently as HA did and, after brief exposure to an acidic environment, induced the fusion of erythrocyte and CV-1 cell membranes. However, the behavior of HAG and HAgC at the cell surface differed from that of HA in several important respects. HAG and HAgC were observed to collect in coated pits whereas wild-type HA was excluded from those structures. In the presence of chloroquine, which inhibits the exit of receptors from endosomes, HAG and HAgC accumulated in intracellular vesicles. By contrast, chloroquine had no effect on the location of wild-type HA. HAG and HAgC labeled at the cell surface exhibited a temperature-dependent acquisition of resistance to extracellular protease at a rate similar to the rates of internalization observed for many cell surface receptors. HA acquired resistance to protease at a rate at least 20-fold slower. We conclude that HAG and HAgC are efficiently routed into the endocytic pathway and HA is not. However, like HA, HAG was degraded slowly, raising the possibility that HAG recycles to the plasma membrane.

Animals↗
PubMed1986

Analysis of progressive deletions of the transmembrane and cytoplasmic domains of influenza hemagglutinin.

Site-directed oligonucleotide mutagenesis has been used to introduce chain termination codons into the cloned DNA sequences encoding the carboxy-terminal transmembrane (27 amino acids) and cytoplasmic (10 amino acids) domains of influenza virus hemagglutinin (HA). Four mutant genes were constructed which express truncated forms of HA that lack the cytoplasmic domain and terminate at amino acids 9, 14, 17, or 27 of the wild-type hydrophobic domain. Analysis of the biosynthesis and intracellular transport of these mutants shows that the cytoplasmic tail is not needed for the efficient transport of HA to the cell surface; the stop-transfer sequences are located in the hydrophobic domain; 17 hydrophobic amino acids are sufficient to anchor HA stably in the membrane; and mutant proteins with truncated hydrophobic domains show drastic alterations in transport, membrane association, and stability.

Amino Acid Sequence↗
PubMed1985

Mutations in the cytoplasmic domain of the influenza virus hemagglutinin affect different stages of intracellular transport.

Mutations have been introduced into the cloned DNA sequences coding for influenza virus hemagglutinin (HA), and the resulting mutant genes have been expressed in simian cells by the use of SV40-HA recombinant viral vectors. In this study we analyzed the effect of specific alterations in the cytoplasmic domain of the HA molecule on its rate of biosynthesis and transport, cellular localization, and biological activity. Several of the mutants displayed abnormalities in the pathway of transport from the endoplasmic reticulum to the cell surface. One mutant HA remained within the endoplasmic reticulum; others were delayed in reaching the Golgi apparatus after core glycosylation had been completed in the endoplasmic reticulum, but then progressed at a normal rate from the Golgi apparatus to the cell surface; another was delayed in transport from the Golgi apparatus to the plasma membrane. However, two mutants were indistinguishable from wild-type HA in their rate of movement from the endoplasmic reticulum through the Golgi apparatus to the cell surface. We conclude that changes in the cytoplasmic domain can powerfully influence the rate of intracellular transport and the efficiency with which HA reaches the cell surface. Nevertheless, absolute conservation of this region of the molecule is not required for maturation and efficient expression of a biologically active HA on the surface of infected cells.

Animals↗
PubMed1985

Radiocesium levels in Irish Sea fish and the resulting dose to the population of the Irish Republic.

Discharges of radioactive materials from the nuclear fuel reprocessing plant at Sellafield in the United Kingdom give rise to 137Cs and 134Cs in fish caught in the Irish Sea. Measurements made on fish catches landed in the Irish Republic show average activities of 68 and 3 Bq/kg (wet) of 137Cs and 134Cs, respectively. The estimated population dose to the Irish public is approximately 2 man-Sv y-1 and the possible dose to a member of the critical group is 1.4% of the limit recommended by the International Commission on Radiological Protection.

Animals↗
PubMed1983

Time-dependency and static mechanics of immature airways and saccules.

Immature rabbit lungs were inflated, then deflated from the fetal pulmonary fluid (FPF)-filled state. Stereomicroscopic observation and measurement of volume change (delta V) during each pressure step and after 15 and 120 sec at each pressure revealed the following: (1) Only airways inflate from atmospheric pressure (P0) to P25. Significant time-dependency here is due to FPF flow through the narrowest airways, airways dilation and recruitment as functions of tissue and surface forces, and, perhaps, interfacial adsorption of surfactants. (2) Saccular recruitment and distention are the principal transformations from P30 to P35. Time-dependency here is the result of FPF flow and labile bubble production. (3) Time-dependency during deflation from P25 to P10 is due to diminishing influence of inflation processes and to decreasing radii of curvature at air/liquid interfaces as FPF refills the saccular air-spaces. Redistribution of air and hypophase liquid probably also play a role. (4) Deflation from P10 to P0 is determined by FPF flow through the smallest airways, interfacial forces, and recoil of previously distended airways as liquid locks are formed. Some implications are that FPF flow through the smallest airways is a gate to saccular ventilation; time-dependent processes place airspaces at risk to rupture; and different time constants of saccules and airways renders 120 sec pressure steps adequate for evaluation of the latter but not the former.

Animals↗
PubMed1981

Functional anatomy and volume-pressure characteristics of immature lungs.

The mechanical behavior of immature rabbit fetal lungs in situ was assessed by air and saline volume-pressure diagrams. All lungs were in their natural fetal state, i.e., filled with fetal pulmonary fluid, prior to inflation. Anatomic correlates were determined by continuous stereomicroscopic monitoring of the lungs. We found the following to be characteristic of immature lungs: (1) Tissue retractive forces are similar to adults. (2) Fetal lungs are not 'plastic' above functional residual capacity. (3) Initial aeration is by 'axial filling' in which airways are distended several times their resting size. (4) Invariably, peripheral rather than central saccules are the first to be aerated and saccules are recruited by both pressure- and time-dependent processes. (5) Pressure-dependence is related to surface forces and terminal orifice size, while time-dependent processes include orifice enlargement, liquid flow through terminal conduits, and the formation of very short-lived, labile bubbles. (6) 'Opening pressure' inflection in the VP diagram is not coincidental with, but follows the onset of saccular aeration. (7) Negative compliance at the onset of deflation is due to saccular enlargement and recruitment. (8) Hysteresis is due to tissue conformational characteristics at high pressures and air entrapment at low pressures. (9) Surface tension cannot be measured reliably from the saline and air VP diagrams.

Animals↗
PubMed1978

Surgical resection for pulmonary interstitial emphysema in the newborn infant.

Three patients with pulmonary interstitial emphysema are presented in whom the course was similar and progressive. Eventually all three infants developed respiratory insufficiency and chronic dependence on mechanical ventilation, cardiovascular complications of patent ductus arteriosus with congestive heart failure, and seizures probably secondary to intermittent periods of asphyxia and hypoxemia. All infants underwent lobectomy and recovered rapidly. Follow-up examinations have shown some residual pulmonary abnormalities. All three infants are progressing within the normal range for motor development.

Follow-Up Studies↗