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D Coleman

Publications and source records attributed to D Coleman.

At least 91 records · Page 5Linked to original sources
PubMed1990

Cilofungin (LY121019) shows nonlinear plasma pharmacokinetics and tissue penetration in rabbits.

We studied the plasma pharmacokinetics and tissue penetration of cilofungin (LY121019), a new echinocandin antifungal compound, by intermittent and continuous infusion in rabbits. Following a single intravenous dose of 50 mg/kg of body weight, the maximum concentration in plasma was 297 +/- 39 micrograms/ml, the area under the curve was 30.1 +/- 6.7 micrograms.h/ml, clearance was 30 +/- 10 ml/min/kg, volume of distribution was 0.85 +/- 0.23 liters/kg, half-life in distribution phase was 3.7 +/- 0.2 min (first 12 min postdose), and half-life in elimination phase was 12.9 +/- 0.7 min. When rabbits received cilofungin by continuous infusion (CI) at 10 mg/kg/h over 6 days, sustained concentrations in plasma of 290 +/- 56 micrograms/ml were seen, more than 50-fold higher than predicted if kinetics were linear. Similarly, at 5 mg/kg/h, high levels were also obtained. Such elevated levels in plasma would not have been predicted from the pharmacokinetic characteristics of cilofungin given as a single intravenous dose. Further pharmacokinetic study at several rates of CI suggested that cilofungin elimination follows Michaelis-Menten kinetics. Simultaneous cilofungin levels in plasma and tissue were then determined for rabbits receiving six intravenous, intermittent doses (ID) of cilofungin at 15 mg/kg every 4 min and for rabbits receiving CI as described above. After ID, the mean of the ratios of cilofungin levels in tissue to those in plasma were highest for liver and bile but very low for cerebrum and cerebellum. After CI, ratios were as much as 89 times higher than for ID and significantly greater in the brain, choroid, kidney, and bile (P less than 0.05). We conclude that following a single dose of cilofungin, the compound is rapidly cleared via first-order kinetics and does not penetrate into the central nervous system, whereas following CI, cilofungin exhibits nonlinear saturable kinetics, is slowly cleared, and significantly penetrates into central nervous system tissues.

Animals↗
PubMed1989

Cloning and characterisation of the serC and aroA genes of Yersinia enterocolitica, and construction of an aroA mutant.

A gene library of Yersinia enterocolitica 8081 was constructed in the cosmid vector pHC79. Recombinants containing the aroA gene, encoding 5-enolpyruvylshikimate 3-phosphate synthase, were identified by complementation of the aroA mutation in Escherichia coli K-12 strain AB2829. All six recombinant plasmids which complemented aroA also complemented the serC mutation in E. coli K-12 strain KL282. Tn5 mutagenesis suggested serC encoding 3-phosphoserine aminotransferase was the proximal gene in an operon with aroA. The nucleotide sequence of a 3-kb HindII-EcoRV fragment encoding the two genes was determined. The serC and aroA open reading frames contain 362 and 428 codons, respectively, and the deduced amino acid sequences share 78% and 81% homology, respectively, with the corresponding E. coli genes. Sequence inspection revealed no obvious terminators or promoters in the intergenic region. The cloned Y. enterocolitica aroA gene was inactivated in vitro and reintroduced into the parental Y. enterocolitica 8081 strain using the suicide vector pJM703.1. Stable aroA insertion mutants of Y. enterocolitica were isolated.

3-Phosphoshikimate 1-Carboxyvinyltransferase↗
PubMed1988

Keratinocyte derived T-cell growth factor (KTGF) is identical to granulocyte macrophage colony stimulating factor (GM-CSF).

Keratinocyte derived T-cell growth factor was initially described as a product of cultured neonatal keratinocytes and keratinocyte cell lines that induced the proliferation of HT-2 cells, a murine T-cell line that responds to IL-2 and IL-4 by incorporating 3H-Thymidine. Subsequently, KTGF has been purified to high specific activity and found to be distinct from IL-2 and IL-4 by a variety of biochemical, immunologic, and immunochemical criteria. Because it was found that certain HT-2 cell lines also proliferated in response to GM-CSF, the present study asked whether KTGF was related to GM-CSF. In this study, we demonstrate that antibodies to recombinant murine GM-CSF completely neutralize the capacity of KTGF to induce HT-2 proliferation without interfering with IL-2 or IL-4 induced HT-2 proliferation. Furthermore, poly-A+ RNA homologous to murine GM-CSF cDNA as judged by S1 nuclease analysis was detected in Pam 212 cells, and protein serologically homologous to GM-CSF was found in Pam 212 conditioned medium. We conclude that KTGF is identical to GM-CSF. The T-cell activating properties of GM-CSF require further exploration.

Colony-Stimulating Factors↗
PubMed1987

Growth of an interleukin 2/interleukin 4-dependent T cell line induced by granulocyte-macrophage colony-stimulating factor (GM-CSF).

Lymphokine activities in conditioned medium from activated helper T cell lines are most commonly defined by the proliferation of "specific" lymphokine-dependent cell lines. Various sublines of IL 2-dependent (and ostensibly specific) HT-2 and CTLL cells have now been shown to proliferate in response to BSF-1/IL 4 as well. After activation with antigen or mitogen, D10.G4.1, an antigen-specific cloned T helper cell that has recently been shown to produce IL 4 but not IL 2, secretes two distinct cytokines that induce the growth of HT-2 cells. These "T cell growth factors" (TCGF) can be separated by reversed phase high-performance liquid chromatography (RP-HPLC). The TCGF activity of one of these factors can be blocked by 11B11, an antibody specific for IL 4. The second TCGF activity is not affected by 11B11 or by antibodies specific for IL 2. This TCGF activity can be neutralized by a goat polyclonal antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF), and has a RP-HPLC elution profile identical to that of recombinant GM-CSF. Recombinant GM-CSF induces both proliferation and long-term growth of HT-2 but not CTLL cells, and this activity can be neutralized by the same antibody to GM-CSF. GM-CSF is best known as a factor that induces the maturation and growth of granulocytes and macrophages from bone marrow-derived hematopoietic precursor cells. The ability of GM-CSF to induce the growth of certain T cell lines indicates that this molecule may play a role in T cell-mediated immune responses, either as an autocrine growth factor or a paracrine stimulus from both lymphoid and nonlymphoid tissues that produce this cytokine.

Animals↗
PubMed1987

Further assessment of the effects of occupational radiation exposure in the United Kingdom Atomic Energy Authority mortality study.

The United Kingdom Atomic Energy Authority mortality study was designed to investigate the relation between exposure to ionising radiation and mortality among the authority's employees. The present paper describes some of the problems encountered in assessing occupational exposure to low dose radiation and examines whether the study's conclusions about the relation between exposure and mortality could be affected by the methods used. The study covered the years 1946 to 1979 during which time the frequency with which personal film dosimeters were issued changed from weekly to monthly, and the threshold level below which measurements were not made decreased 20-fold. Exposure from "below threshold" readings made an important contribution to total exposure in the early years. Estimates, based on the remeasurement of a sample of old films, indicated that the average whole body exposure before 1961 may have been about double that which was measured. Furthermore, although records were kept of when dosimeters were lost or damaged, the associated exposures were unknown and could only be estimated. Workers whose dosimeter readings were missing for more than 5% of the time during which they were monitored had higher all cause mortality (p = 0.04) and higher mortality from accidents and violence (p = 0.05) than other radiation workers. The results of analyses of mortality in relation to whole body exposure were compared when the exposures included estimates of the below threshold and missing exposures and when these exposures were assumed to be zero. Some of the findings differed, but none changed sufficiently to alter the general conclusions. Although the trend in mortality from all cancers changed from one in which the increase with exposure was far from statistically significant (p = 0.3) when the below threshold and missing values were assumed to be zero to one that approached significance (p = 0.06) after they were estimated, calculations of the annual excess deaths from cancer per unit dose resulted in broadly similar estimates. Studies of workers exposed to ionising radiation usually focus on mortality in relation to whole body exposure. In the present paper its relation to neutron and surface exposure is also examined. Workers with measured neutron exposures had significantly lower all cause mortality than other workers with a radiation record (p = 0.03). Surface exposure was significantly related to mortality from all cancers (p = 0.02) and prostatic cancer (p less than 0.001). Some data on cancer registration are presented but these cannot be readily interpreted because cancer registration details were available only for ex-employees who may not be typical of the workforce as a whole.

Humans↗
PubMed1986

Transabdominal chorionic villus sampling.

Transabdominal chorionic villus sampling, carried out with a fine-bore needle and cannula under ultrasound guidance, was as successful as transcervical aspiration but avoided the risks of bacterial contamination associated with the latter technique. The transabdominal procedure can be carried out under local anaesthesia, and multiple samples can be obtained, if necessary, through a single cannula.

Abdomen↗
PubMed1986

Managing the behavior of adults with autism in the job setting.

The purpose of the study was to facilitate the adjustment of adults who are severely disabled by autism to the job setting. Three cases are presented that illustrate the use of on-the-job training procedures to manage behavior problems of adults with autism. In two cases aggressive and oppositional behavior were eliminated or reduced in frequency, and in a third case production rate was increased. The feasibility of on-the-job training of adults with autism is discussed, and expanded research into vocational training programs is recommended.

Adult↗
PubMed1986

The challenge of AIDS.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Methicillin-resistant Staphylococcus aureus in Dublin 1971-84.

Between 1971 and 1975, methicillin-resistant Staphylococcus aureus (MRSA) caused sporadic infection in eight Dublin hospitals although a case of bacteraemia was not recorded until 1976. From then on gentamicin-resistant MRSA rapidly became endemic in Dublin hospitals. The frequency of MRSA bacteraemia reached a peak in 1979-82 but MRSA infection remains an important problem. The most effective antimicrobial agent in treatment of invasive infection was vancomycin; little drug toxicity was seen. Where appropriate, concomitant surgical treatment such as debridement and drainage was usually necessary. Infection control measures directed at eliminating carriage proved effective in reducing spread. Molecular analysis showed two distinct MRSA phenotypes with similar phage-typing patterns. Gentamicin resistance was chromosomally encoded.

Gentamicins↗
PubMed1985

Mortality of employees of the United Kingdom Atomic Energy Authority, 1946-1979.

An analysis was conducted of 3373 deaths among 39 546 people employed by the United Kingdom Atomic Energy Authority between 1946 and 1979, the population having been followed up for an average of 16 years. Overall the death rates were below those prevailing in England and Wales but consistent with those expected in a normal workforce. At ages 15-74 years the standardised mortality ratios (SMRs) were 74 for deaths from all causes and 79 for deaths from all cancers. Mortality from only four causes was above the national average--namely, testicular cancer (SMR 153; 10 deaths), leukaemia (SMR 123; 35 deaths), thyroid cancer (SMR 122; three deaths), non-Hodgkin's lymphoma (SMR 107; 20 deaths)--but in none was the increase significant at the 5% level. Half of the authority's employees were recorded as having been monitored for exposure to radiation, their collective recorded exposure being 660 Sv (65 954 rem). Among these prostatic cancer was the only condition with a clearly increased mortality in relation to exposure. Of the 19 men who had a radiation record and died from prostatic cancer at ages 15-74 years, nine had been monitored for several different sources of exposure to radiation. The standardised mortality ratios were 889 (six deaths) in employees monitored for contamination by tritium, 254 (nine deaths) in those monitored for contamination by other radionuclides, and 385 (nine deaths) in those with dosimeter readings totalling more than 50 mSv (5 rem); but the same nine subjects tended to account for each of these significantly raised ratios. Because multiple exposures were common and other relevant information was not available the reason for the increased mortality from prostatic cancer in this population could not be determined and requires further investigation. Excess mortality rates of 2.2 and 12.5 deaths per million person years per 10 mSv (1 rem) were estimated for leukaemia and all cancers, respectively. The confidence limits around these estimates were wide, included zero, and made it unlikely that the International Commission on Radiological Protection's cancer risk coefficients were underestimated by more than 15-fold. Thus despite this being the largest British workforce whose mortality has been reported in relation to low level ionising radiation exposure, even larger populations will need to be followed up over longer periods before narrower ranges of risk estimates can be derived.

Adolescent↗
PubMed1985

Chylomicron remnant and asialoglycoprotein metabolism are independent.

Because of the considerable similarities between the hepatic metabolism of chylomicron remnants and asialoglycoproteins, the hypothesis that they might share a cell surface receptor or a common step in internalization was tested. Unlabeled chylomicron remnants did not reduce the binding of 125I-asia-glycoprotein to plasma membranes, but did compete for 125I-chylomicron remnant binding. The converse also was true. This suggested the receptors were distinct. The two substances did not compete with each other for removal by the isolated perfused rat liver. This suggests that no potentially common post binding events can become rate limiting. In conclusion, despite similarities in their removal and metabolism, chylomicron remnants and asialoglycoproteins are metabolized independently.

Animals↗
PubMed1985

Expression of a gene for glucan-binding protein from Streptococcus mutans in Escherichia coli.

The structural gene for a glucan-binding protein (GBP) of Streptococcus mutans has been inserted into a bacteriophage lambda vector and expressed in Escherichia coli K12. Lysates of E. coli infected with the recombinant phage contain an antigenic protein of the same size as S. mutans GBP. The GBP synthesized in E. coli can be affinity-purified on immobilized glucan and antiserum raised against it has been shown to precipitate fructosyltransferase activity from S. mutans.

Antigens, Bacterial↗
PubMed1985

Investigation into the value of Papanicolaou stained cervical smears for the diagnosis of chlamydial cervical infection.

Forty five (37%) of 121 female contacts of men with non-gonococcal urethritis or gonorrhoea were chlamydia positive, as judged by isolation or by detecting elementary bodies in smears with a fluorescein labelled chlamydial monoclonal antibody. Only six (13%) of these, however, had Papanicolaou stained smears in which there were inclusion like changes suggestive of chlamydial infection. Furthermore, of 15 patients who had such cytological changes, chlamydiae were detected in only six and the abnormalities were found also in Papanicolaou stained smears from 10 (13%) of the 76 chlamydia negative patients. Modifying the Papanicolaou stained smears by including endocervical material did not increase sensitivity. In addition, destaining and restaining them with the monoclonal antibody was time consuming and the results were unreliable. The staining of cervical smears with Papanicolaou reagent is a technique of low sensitivity and specificity for diagnosing or screening for chlamydial cervical infection and cannot be recommended.

Cervix Mucus↗