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Biomedical subjects

S Dawson

Publications and source records attributed to S Dawson.

At least 73 records · Page 4Linked to original sources
PubMed1999

Circadian interrelationships among levels of plasma fibrinogen, blood platelets, and serum interleukin-6.

Circadian (24 h) rhythms of fibrinogen, interleukin-6 (IL-6), and platelet levels were studied in 11 males ages 46 to 72 years. Since there is a known circadian rhythm for fibrinogen and IL-6, we postulated that the peak level (acrophase) of fibrinogen would follow the acrophase of IL-6, based on the fact that IL-6 is the stimulus for fibrinogen production in the liver. Platelet levels were measured to show whether there was any correlation with the IL-6 acrophase because it has been reported that IL-6 affects megakaryocytes and platelets in dogs. We found that the acrophase for IL-6 occurred at 02:03 h and the acrophase for fibrinogen occurred at 09:16 h. Platelet counts peaked at 16:56 h. Thus, there was a positive correlation between IL-6 and fibrinogen acrophases and a negative correlation of each with the acrophase for platelets. The positive linkage of IL-6 with fibrinogen in this study suggests that suppression of IL-6 production would lower those peak fibrinogen levels that occur in the morning in association with arterial ischemic events. This could result in fewer arterial ischemic events, especially in the morning.

Aged↗
PubMed1998

Transcutaneous monitoring of blood gases: is it comparable with arterialized earlobe sampling?

Researchers are increasingly looking for reliable non-invasive methods of assessing blood gas concentrations, and several new techniques have recently become available. Values derived using arterialized earlobe samples have been found to be comparable with conventional arterial samples, and recent studies have compared transcutaneous blood gas analysis with the traditional arterial samples and found a reasonable level of agreement in particular for the partial pressure of carbon dioxide. There are no data comparing oxygen and carbon dioxide partial pressures (pO2, pCO2) derived from arterialized samples with one of the newer transcutaneous techniques. We therefore simultaneously studied arterialized earlobe blood gas samples and values for pO2 and pCO2 obtained by a transcutaneous monitor (TINA, Radiometer, Copenhagen) in 26 subjects with varying blood gas values. There was a close agreement between the two methods for assessment of pCO2 [mean difference (95% C.I.) between transcutaneous and earlobe values 0.25 kPa (-0.004, 0.5 kPa)], but not for pO2 [1.71 kPa (0.35, 3.07 kPa)]. Similarly, the limits of agreement were narrow for pCO2 compared to those for pO2 (-0.98, 1.47 kPa and -6.44, 3.02 kPa respectively). We conclude that transcutaneous measurement of pCO2 using the TINA is acceptable in the research setting, whereas assessment of pO2 cannot reliably be made using this technique.

Adult↗
PubMed1998

The use of pulsed-field gel electrophoresis to examine the epidemiology of Bordetella bronchiseptica isolated from cats and other species.

A collection (164) of isolates of Bordetella bronchiseptica made predominantly from cats (132) but also from dogs (15), pigs (12) and other species was examined by pulsed field gel electrophoresis following macrorestriction digestion with XbaI. Each isolate was analysed twice and the patterns were entirely reproducible. The isolates fell into 17 different strains (> 3 bands different) and within strains there were numerous subtypes. Feline isolates fell into 12 of the 17 strains. In general, cats housed together had similar or identical strains and subtypes of B. bronchiseptica. There was no difference in the PFGE patterns of isolates made from carrier cats and those from cats with respiratory disease. Isolates from pigs and dogs were in general similar to the feline isolates and there was no great evidence for species specificity. The PFGE pattern of feline and canine isolates were more related to whether the animals were housed together rather than whether they came from dogs or cats.

Animals↗
PubMed1998

Women in a prenatal care/substance abuse treatment program: links between domestic violence and mental health.

OBJECTIVES: This study examines the prevalence of violence experienced by patients enrolled in the Step by Step program, a combined prenatal care/substance abuse treatment program at the Wake County Health Department in North Carolina. In addition, potential associations between violence and sociodemographic characteristics, substance use, and mental health are investigated. METHOD: All prenatal care/substance abuse treatment patients who met study eligibility criteria (N = 84) were assessed by health care providers. Descriptive statistics and bivariate analyses were used to compare victims of violence and nonvictims on a wide range of variables. Multiple linear regression analysis estimated the impact of the women's experiences of violence on their levels of mental health symptoms while controlling for confounding factors. RESULTS: Forty-two percent of patients had been victims of both sexual and physical violence, and 30% had been victims of physical violence alone. The combination of sexual and physical violence was significantly less common among African-American women compared with other women. No other significant differences were found between victims and nonvictims in terms of sociodemographics or substance use. Compared with nonvictims, victims of the combination of sexual and physical violence had significantly elevated levels of general psychological distress as well as elevated levels of hostility, depression, anxiety, interpersonal sensitivity, and somatization. However, no significant differences in levels of mental health symptoms were observed among women who had experienced physical violence in the absence of sexual violence. CONCLUSIONS: Questions concerning experiences of violence, including sexual victimization, should be incorporated into the clinical history-taking procedures of professionals working within prenatal care/substance abuse treatment programs so that effective interventions that take experiences of violence into account can be put into place for these high-risk women.

Adult↗
PubMed1998

Quasispecies evolution of a hypervariable region of the feline calicivirus capsid gene in cell culture and in persistently infected cats.

Feline calicivirus (FCV) is a respiratory pathogen of cats that is capable of causing persistent infections. This study examined the evolution of a hypervariable region of the FCV capsid gene both during 90 passages in cell culture and during replication in persistently infected cats. This region of the capsid protein is known to contain neutralization epitopes and may be a target for immune evasion during virus persistence in the host. Sequence analysis showed that FCV exists as a quasispecies which evolved both in cell culture and in persistently infected cats. Changes involved both loss of sequence present in the infecting isolate and a gain of both synonymous and non-synonymous nucleotide substitutions to generate sequences not detected within earlier isolates. Overall, these changes led to a reduction in population heterogeneity over time. Where virus populations were highly homogeneous allowing a consensus sequence to be determined, evolution rates for the consensus sequence ranged from 0.10-1.07 substitutions per nucleotide per year. Marked changes in virus neutralization profiles were seen in isolates obtained sequentially from a persistently infected cat. This was not the case with cell culture passaged virus, suggesting that the individual amino acid changes found only in virus from persistently infected cats may significantly alter the antigenic profile of FCV, and may be the result of immune selection.

Amino Acid Sequence↗
PubMed1998

The formation of ceramide from sphingomyelin is associated with cellular apoptosis.

The apoptotic response of the immature B-cell to the cross-linking of surface IgM receptors provides a good model for cell death and we show in WEHI-231 B-cells that the time course of apoptosis corresponds to the increased formation of ceramide, as measured either by mass (using the diacylglycerol kinase method) or radiolabelling with [3H]palmitate. Inhibitors of sphingosine biosynthesis have no effect on cell death induced by anti-IgM in WEHI-231 but inhibitors of ceramidase accelerate apoptosis, suggesting that activation of sphingomyelinase is the key event in apoptosis. We have demonstrated this by in vitro assay of neutral sphingomyelinase. Apoptosis is also important in normal brain development and neuronal survival is dependent upon phosphatidylinositol 3-kinase (PI3-kinase) activation by growth factors (insulin, nerve growth factor etc.). Withdrawal of these growth factors or inhibition of PI3-kinase with wortmannin or LY294002 activated the pro-apoptotic CPP32 (Yama/Apopain/caspase 3, EC 3.4.22), activated neutral sphingomyelinase and increased ceramide formation in an immortalized dorsal root ganglion cell line F-11. Protection against apoptosis can be achieved by overexpression of the bc12 family of proteins or addition of drugs which elevate cAMP levels. cAMP protects against apoptosis induced by either wortmannin or staurosporine. The specificity for cAMP was confirmed by showing protection with the specific agonist (Sp)cAMPS and increased killing with the antagonist (Rp)cAMPS. However, cAMP did not protect against ceramide killing, suggesting that there are at least two major pathways of apoptosis in neuronal cells.

Animals↗
PubMed1997

Pravastatin increases survival and inhibits natural killer cell enhancement factor in liver transplanted rats.

Pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has been shown to decrease the number of acute rejection episodes in cardiac and renal transplant patients. This study evaluates the effects of pravastatin on survival of rats following liver transplant and attempts to elucidate the mechanisms of these effects. Both survival and natural killer cell enhancing factor (NKEF) studies utilized Dark Agouti rats for donor livers transplanted into Brown Norway rats as recipients. All rats received daily low-dose cyclosporine (CsA) 2 mg/kg/day by gavage. The treated groups also received gavage doses of pravastatin, 20 mg/kg/day. Survival data were analyzed by the method of Kaplan-Meier and log-rank chi 2 tests for statistical significance. For NKEF evaluation, rats were sacrificed at varying time points; total RNA was extracted from the liver and hybridized with 32P-radiolabeled NKEF DNA probes in the Northern blot technique. Radiographs were quantitated using densitometry. Data were analyzed by two-way ANOVA. Actuarial survival was improved (P < < 0.05) in rats treated with pravastatin in addition to low-dose CsA (n = 41, CsA alone n = 74). Less fibrosis and chronic rejection was seen on histological section in the treated animal livers, P < 0.05, NKEF was seen maximally at Days 5-15 tapering off at Day 21. NKEF-a and NKEF-b levels were significantly decreased in the animals treated with CsA and pravastatin compared to CsA alone in the group of animals < 16 days postop (P < < 0.05). Pravastatin improves survival in rats following OLT and while the mechanism is still unknown, inhibition of natural killer cell enhancement factor may represent an alteration in the overall immune response.

Animals↗
PubMed1997

Antimicrobial susceptibility of Bordetella bronchiseptica isolates from cats and a comparison of the agar dilution and E-test methods.

One hundred and fifty-two predominantly feline isolates of Bordetella bronchiseptica were tested for their susceptibility to seven antimicrobial agents using an agar dilution method. The majority of isolates tested by the agar dilution method were resistant to trimethoprim (MIC90 500 micrograms/ml) and ampicillin (MIC90 > 32 micrograms/ml) but sensitive to tetracycline, doxycycline and enrofloxacin (MIC90 2 micrograms/ml for all three agents). The isolates showed a spectrum of susceptibility to sulphadiazine and clavulanate potentiated amoxycillin. The MIC's of twenty-nine of the 152 isolates were then compared for five of the antimicrobial agents using the E-test (AB Biodisk, Sweden), a recently introduced method for measuring the MIC's of antimicrobial agents based on the diffusion of a pre-defined antibiotic gradient from a plastic strip. Comparisons with the E-test demonstrated an overall agreement (+/- 1 log2 dilution) with the agar dilution method of 79.4% and an agreement within +/- 2 log2 dilutions of 96.2%.

Agar↗
PubMed1997

The 26S-proteasome: regulation and substrate recognition.

There is extensive reprogramming of the ATPase regulators of the 26S proteasome before the programmed elimination of the abdominal intersegmental muscles (ISM) after eclosion in Manduca sexta [1]. This extensive ATPase reprogramming only occurs in ISM which are destined to die and not in flight muscle (FM). The MS73 ATPase also increases in the proleg retractor muscles which die at a developmentally different stage to ISM. The non-ATPase regulator S5a shows a similar increase to the ATPase regulators. We have cloned the Manduca SUG2 ATPase and shown that this ATPase is a component of the 26S proteasome. This ATPase shows a similar increase in concentration to the other ATPases in 26S proteasomes before muscle death. The SUG2 ATPase is also associated with other smaller complexes besides the 26S proteasome which act as activators of the 26S proteasome. Finally, in a yeast two-hybrid genetic screen we have identified a protein in human brain which interacts with the MS73 ATPase (and human S6). The interacting protein contains 6 ankyrin repeats and is co-immunoprecipitated with anti-MS73 antiserum after in vitro transcription/translation. The ankyrin repeat protein may interact with the MS73 ATPase as part of the substrate recognition process by the 26S proteasome. Many proteins degraded by the 26S proteasome contain ankyrin repeats, e.g. IkB and some cyclins: binding through ankyrin repeats to an ATPase regulator may complement protein ubiquitination and S5a binding as recognition signals by the 26S proteasome.

Abdominal Muscles↗
PubMed1997

Characterization of antibiotic resistance plasmids from Bordetella bronchiseptica.

Of 52 antibiotic-resistant Bordetella bronchiseptica isolates from cats, ten carried plasmids. Only two of these plasmids, pLV1400 and pLV1401, were self-transmissible to Escherichia coli K12; both plasmids encoded resistance to ampicillin, tetracycline, sulphonamides, streptomycin and mercuric chloride, and were of incompatibility group P (IncP). Transferable tetracycline resistance has not been reported in B. bronchiseptica previously. The plasmids were identical in size (c.51 kb), restriction endonuclease digestion pattern and gene sequences (trfA and korA) within the IncP replicon. The trfA and korA sequences differed from those of the archetypal IncP plasmids RP4 and R751. Although the two B. bronchiseptica isolates were from epidemiologically and geographically separated cats, pulsed-field gel electrophoresis of their XbaI- or DraI-digested chromosomal DNA indicated that they were genotypically identical. The plasmid-encoded ampicillin resistance was mediated by a penicillinase of molecular weight 49,000, and pI 8.45 which was inhibited by clavulanate (IC50 = 0.1 mg/L) and tazobactam (IC50 = 0.42 mg/L) but not by parachloromercuribenzoate or EDTA. The high-level tetracycline resistance was mediated by a class C efflux mechanism that has not been described previously in this genus. The presence of transferable multi-drug resistance on a promiscuous plasmid may limit options for therapy of respiratory tract infection in companion and farm animals.

Animals↗
PubMed1997

Transforming the National Health Service. The challenge for career management.

Claims that, for the 1990s, images of careers are multidimensional and individualistic. Notes that employees are encouraged to take responsibility for their own self-development, incorporate horizontal as well as vertical moves and forge careers based on "employability", i.e. learning, networking and reputation. Bases its arguments on the findings of a study into senior executives in the NHS, and explores the consequences of organizational restructuring for the careers of clinical, general and functional managers. Suggests that organizational and professional barriers exist to undermine the notion of the multidimensional career. Argues that prescriptive approaches to career self-development need to take account of organizational context and that, to meet the challenges of careers in the 1990s, both the organization and the individual need to become more willing to take risks.

Attitude of Health Personnel↗
PubMed1996

Specific developmental changes in the regulatory subunits of the 26 S proteasome in intersegmental muscles preceding eclosion in Manduca sexta.

Previously, we have shown extensive reprogramming of the ATPase regulator of the 26S proteasome preceding the programmed destruction of intersegmental muscles (ISM) in the tabacco horn moth Manduca sexta (Dawson et al., J. Biol. Chem, 270, 1850-1858, 1995). We now show that the extensive reprogramming of the regulatory components of the 26S proteasome occurs only in ISM and not in flight muscles (FM), which undergo terminal differentiation at ecdysis. Unlike in ISM, the ATPase regulators, MS73, MSS1, TBP1 and mts2, remain at low levels in 26S proteasomes in FM from developmental Stage-0 to Stage-7. The non-ATPase regulator subunit 5a, which binds to multiubiquitin chains, increased in ISM similarly to the ATPases but not in FM. The ecdysteroid agonist RH-5849 prevented these subunit increases in ISM. These findings show that reprogramming of 26 S proteasomes is involved in the specific elimination of ISM during eclosion and does not occur in FM which are needed for adult moth flight.

Animals↗
PubMed1996

Hyperlipidemia after liver transplantation: natural history and treatment with the hydroxy-methylglutaryl-coenzyme A reductase inhibitor pravastatin.

This study was designed to determine the frequency of hyperlipidemia after orthotopic liver transplantation and whether treatment with a hydroxy-methylglutaryl coenzyme A reductase inhibitor was safe and efficacious. Cholesterol levels were assessed in 45 consecutive adult liver transplants (mean +/- SE). Four of 22 patients on cyclosporine (CsA) (18%) and three of 23 patients on FK506 (13%) had levels >225 mg/dl at 12 months (cholesterol levels for patients on CsA [total n=22]: pre-Tx = 140+/-11, 1 month = 183+/-36,3 months = 221+/-12, 6 months = 211+/-11, 12 months = 202+/-14 [P<0.01 vs. pre-Tx]; FK506 [total n=23]: Pre-Tx = 151+/-13, 1 month = 187+/-22, 3 months = 188+/-10, 6 months = 184+/-13, 12 months = 164+/-9 [P=0.02 vs. CsA]). A separate cohort of patients with stable graft function, cholesterol >225 mg/dl, and two additional risk factors for coronary artery disease were started on pravastatin. Ninety-eight patients were enrolled. Sixteen patients (16%) discontinued the drug because of subjective complaints. No episodes of rhabdomyolysis or hepatotoxicity occurred (cholesterol levels for patients on CsA [total n=65]: pretreatment = 251+/-7, 6 months = 220+/-7 [P=0.01 vs. pretreatment], 12 months = 224+/-8 [P=0.01 vs. pretreatment]; FK506 [total n=17]: pretreatment = 251+/-17, 6 months = 219+/-17, 12 months = 208+/-17 [P=0.08 vs. pretreatment]). Natural killer cells isolated from normal volunteers (n=14) exhibited 27+/-9% specific lysis. Patients on FK506 or cyclosporine-based immunosuppression alone (n=11) exhibited 20+/-4% specific lysis. Standard immunosuppression plus pravastatin (n=10) decreased lysis to 0.2+/-10% (P<0.02 vs. controls and standard immunosuppression). We conclude: (1) posttransplant hyperlipidemia occurs less frequently in liver transplant patients than in renal or cardiac transplants; (2) pravastatin is safe and efficacious for cholesterol reduction in liver transplant patients; and (3) pravastatin coadministered with standard immunosuppression reduces natural killer cell-specific lysis in these recipients.

Adult↗