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Biomedical subjects

S Lawrence

Publications and source records attributed to S Lawrence.

At least 37 records · Page 2Linked to original sources
PubMed2000

Retrotransposition of a bacterial group II intron.

Self-splicing group II introns may be the evolutionary progenitors of eukaryotic spliceosomal introns, but the route by which they invade new chromosomal sites is unknown. To address the mechanism by which group II introns are disseminated, we have studied the bacterial L1.LtrB intron from Lactococcus lactis. The protein product of this intron, LtrA, possesses maturase, reverse transcriptase and endonuclease enzymatic activities. Together with the intron, LtrA forms a ribonucleoprotein (RNP) complex which mediates a process known as retrohoming. In retrohoming, the intron reverse splices into a cognate intronless DNA site. Integration of a DNA copy of the intron is recombinase independent but requires all three activities of LtrA. Here we report the first experimental demonstration of a group II intron invading ectopic chromosomal sites, which occurs by a distinct retrotransposition mechanism. This retrotransposition process is endonuclease-independent and recombinase-dependent, and is likely to involve reverse splicing of the intron RNA into cellular RNA targets. These retrotranspositions suggest a mechanism by which splicesomal introns may have become widely dispersed.

Bacterial Proteins↗
PubMed2000

Cloning and expression, pharmacological characterization, and internalization kinetics of the pituitary GnRH receptor in a metatherian species of mammal.

Gonadotropin-releasing hormone receptors (GnRH-Rs) expressed in the pituitary of eutherian species of mammal are unique in lacking the cytoplasmic C-terminal tail characteristic of GnRH-Rs of nonmammalian vertebrates and other G protein-coupled receptors. To further investigate evolutionary relationships among vertebrate GnRH-Rs, a full-coding region cDNA of the pituitary GnRH-R was cloned from a metatherian marsupial mammal, the Australian brushtail possum (Trichosurus vulpecula). We have determined the pharmacological characteristics and internalization kinetics of this GnRH-R from an early evolved, metatherian species of mammal and compared it with the corresponding receptors in eutherian species of mammal and nonmammalian vertebrates. The predicted GnRH-R protein from the possum pituitary has high homology with the other mammalian GnRH-Rs (80% identity) and, in common with other mammals, lacks an intracellular C-terminal tail. The ligand selectivity of the possum GnRH-R transfected into COS-1 cells, assessed using inositol phosphate assays and radioreceptor binding assays, was similar to that of the other mammalian GnRH-Rs, and distinct from those of the nonmammalian GnRH-Rs. The pharmacological characteristics of the possum GnRH-R were similar to those of other mammalian GnRH-Rs, for a selection of agonists (including naturally occurring GnRH ligands and superagonists) and antagonists. Receptor-mediated internalization of GnRH agonist by the possum GnRH-R was slightly more rapid than that of the human GnRH-R, while the internalization kinetics of the chicken GnRH-R, in which a cytoplasmic C-terminal tail is present, was considerably more rapid. In terms of the evolution of the GnRH-R in vertebrates, the possum (a metatherian mammal) GnRH-R has a striking resemblance, in both structure and pharmacological characteristics, to GnRH-Rs in eutherian mammals, which are quite distinct from the nonmammalian vertebrate GnRH-Rs, and are unique among G protein-coupled receptors in lacking an intracellular C-terminal tail. The distinct structure of the pituitary GnRH-R in mammalian vertebrates is likely to have important functional consequences in the reproductive physiology of mammals.

Amino Acid Sequence↗
PubMed2000

Measurement of the performance of nerve cuff electrodes for recording.

New designs of cuff electrodes for the recording of signals from peripheral nerves are typically tested in acute animal experiments before long-term evaluation takes place. A reproducible, cost-effective and fast method is presented for evaluating cuff electrodes with respect to signal amplitude, noise rejection, and, in some cases, selectivity, as an alternative to acute in vivo experiments. Comparisons with a computer model and with signals obtained from rabbit tibial nerve give good agreement with the new method. It is shown that an imperfect closure of the cuff around the nerve can easily lead to more than 50% loss of the signal amplitude. Noise from sources external to the cuff is not significantly affected by the closing mechanism, but is strongly reduced by a tripolar cuff configuration as compared with a monopolar one (reduction factor 2.8 to 58, mean = 6.5, n = 6). In dual-channel cuffs, cross-talk is below 1.2% indicating a very high selectivity.

Action Potentials↗
PubMed2000

Perfusion method for thoracoabdominal aneurysm repair using the open distal technique.

Challenges related to perfusion support of thoracoabdominal aneurysm repair include maintenance of distal aortic perfusion, rapidity of fluid resuscitation, and avoidance of both hypothermia and excessive hemodilution. Using available technology, we have devised a circuit and protocol that addresses these issues. To accomplish such support a bypass circuit consisting of 3/8 inch tubing connected to a centrifugal pump and low-prime heat exchanger was constructed. The circuit was primed via 1/4 inch spiked connectors attached to a 3-liter bag of normal saline. After initial de-airing, the solution was recirculated through this bag. Patients were anticoagulated with 1 mg/kg of heparin prior to initiation of support. Left atrial-descending aorta bypass was used primarily. A cell salvage device was used for autotransfusion. All blood products were delivered via a rapid infusion device. During partial exsanguination, shed blood was not processed, but directed to the rapid infusor for immediate retransfusion. Any packed cells given were washed prior to transfusion. Citrate dextrose solution was used as an anticoagulant for the cell scavenger. This configuration was used successfully in 50 procedures during an 18-month period. Use of this low-prime, custom circuit reduced both hemodilution and cost. A connection off the cell salvage pump offers fast retransfusion of shed blood during partial exsanguination. Minimal heparinization and citrate anticoagulation appears to reduce coagulopathy.

Adult↗
PubMed1999

Successful obstetric outcome after simultaneous pancreas and kidney transplantation.

A 34-year-old woman became pregnant two years after having a simultaneous pancreas and kidney (SPK) transplantation, necessitated by type 1 diabetes and end-stage renal disease. The pregnancy was uneventful until 30 weeks' gestation, when she developed pancreatitis and a worsening of mild hypertension. A healthy 1700 g boy was delivered by caesarean section at 34 weeks' gestation. This is the first report of a successful pregnancy after SPK transplantation in Australia.

Adult↗
PubMed1999

Usefulness of a state-legislated, comparative database to evaluate quality in colorectal surgery.

PURPOSE: Colorectal surgery, a high-volume procedure, has been targeted for performance improvement to reduce length of stay. Specific postoperative quality indicators and readmission rates should be analyzed concomitantly to assure that adverse events are not associated with earlier discharge. METHODS: From July 1, 1990, to June 30, 1997, 1,218 consecutive patients who underwent transabdominal colorectal surgery were analyzed for length of stay, mortality, morbidity, and discharge disposition. Each patient was assigned an Admission Severity Group rating 0 to 4 using a hospital-based state-legislated software system (Atlas) to validate comparative performance internally and externally. Readmission data within 120 days of discharge were available for the last 678 consecutive patients from July 1, 1993, to June 30, 1997, using Lastword (computerized medical records). RESULTS: The annual frequencies of the 1,218 procedures were 173, 183, 175, 146, 167, 189, and 185, respectively, from July 1990 through June 1997. Severity distribution was 32 for Admission Severity Group 0, 517 for Admission Severity Group 1, 540 for Admission Severity Group 2, 128 for Admission Severity Group 3, and 1 for Admission Severity Group 4, with no annual difference (P = 0.012). There was a significant reduction in total length of stay of 3.1 (12.9-9.8) days during the seven years (P = 0.001). The overall operative mortality rate was 1.4 percent, and the morbidity was 2.6 percent, with no annual differences (P = 0.655 and P = 0.033, respectively). The disposition to home did not change (P = 0.21). Of the 678 patients followed up for readmission, 100 (14.7 percent) were readmitted within 120 days, with no annual difference (P = ().302). CONCLUSION: Mortality, morbidity, disposition, and readmission rates were not affected by a decreased length of stay after colorectal surgery.

Colonic Diseases↗
PubMed1999

Chronic active hepatitis B exacerbations in human immunodeficiency virus-infected patients following development of resistance to or withdrawal of lamivudine.

Lamivudine is a nucleoside analog with activity against human immunodeficiency virus (HIV) and hepatitis B virus (HBV). Patients coinfected with HIV and HBV may have hepatitis flares when lamivudine therapy is discontinued or when resistance of HBV to lamivudine emerges. This retrospective, descriptive study conducted in three tertiary care medical centers describes patients coinfected with HIV type 1 and HBV who presented with a spectrum of clinical and subclinical hepatitic responses to lamivudine withdrawal or resistance. One patient had fulminant hepatic failure and a second patient had subclinical hepatitis when lamivudine therapy was discontinued and a more efficacious antiretroviral regimen was substituted. Three patients had flares of hepatitis after 13 to 18 months of lamivudine therapy. Lamivudine withdrawal or emergence of lamivudine-resistant mutants in patients coinfected with HIV and HBV may result in severe hepatitis. Clinicians caring for patients with coinfection with HIV and HBV should be aware of the possibility that a hepatitis B flare may occur in previously asymptomatic carrier patients.

AIDS-Related Opportunistic Infections↗
PubMed1999

Replacing abdominally implanted defibrillators: effect of procedure setting on cost.

Although most ICDs are currently placed using a pectoral approach, there exists a large population of patients with abdominally implanted ICDs who will require device replacement due to a depleted battery. The purpose of this study was to compare the cost, convalescence, and complication rate of replacing abdominally implanted ICDs in the OR versus the EP laboratory. Between August 1993 and September 1994, we prospectively enlisted nine consecutive patients who presented for their second ICD generator replacement and who had a prior generator replacement in the OR 3-4 years earlier. The mean age of the patients was 63 +/- 17 years and their mean ejection fraction was 37% +/- 15%. ICD replacement was performed in the EP laboratory and consisted of explanting the old device, electronic interrogation of the lead system, and confirmation of defibrillation thresholds prior to implanting a new device. Local anesthesia was provided by lidocaine infiltration and sedation was achieved with intravenous (i.v.) midazolam and fentanyl. Following the procedure, the patients were returned to an outpatient monitored setting for 4 hours and were then discharged. Comparisons of the health care charges for the same procedure performed in the two different settings revealed a significant reduction in physician fees (from $3,621 +/- $556 to $2,179 +/- $577, P < 0.05), in hospital charges (from $5,811 +/- $1,102 to $2,306 +/- 696, P < 0.05), and in total charges (from $9,431 +/- $1,375 to $4,541 +/- $1,010, P < 0.05), exclusive of ICD cost, when the procedure was performed on an outpatient basis in the EP laboratory. Inpatient days averaged 3.0 +/- 0.3 when the procedure was performed in the OR. On long-term follow-up there were no complications following abdominal ICD generator replacement in the OR (mean follow-up, 39 +/- 2 months) or in the EP laboratory (mean follow-up, 42 +/- 4 months). Thus, ICD replacements in the EP laboratory cost less than in the OR due to significantly lower physician fees, hospital charges, and a shorter postprocedural convalescence.

Abdomen↗
PubMed1998

Searching the world wide Web

The coverage and recency of the major World Wide Web search engines was analyzed, yielding some surprising results. The coverage of any one engine is significantly limited: No single engine indexes more than about one-third of the "indexable Web," the coverage of the six engines investigated varies by an order of magnitude, and combining the results of the six engines yields about 3.5 times as many documents on average as compared with the results from only one engine. Analysis of the overlap between pairs of engines gives an estimated lower bound on the size of the indexable Web of 320 million pages.

Journal Article↗
PubMed1998

Altitude training at 2690m does not increase total haemoglobin mass or sea level VO2max in world champion track cyclists.

Haemoglobin mass (Hb mass), maximum oxygen consumption (VO2max), simulated 4000 m individual pursuit cycling performance (IP4000), and haematological markers of red blood cell (RBC) turnover were measured in 8 male cyclists before and after (A) 31 d of altitude training at 2690 m. The dependent variables were measured serially after altitude on d A3-4, A8-9 and A20-21. There was no significant change in Hb mass over the course of the study and VO2max at d A9 was significantly lower than the baseline value (79.3 +/- 0.7 versus 81.4 +/- 0.6 ml x kg(-1) x min(-1), respectively). No increase in Hb mass or VO2max was probably due to initial values being close to the natural physiological limit with little scope for further change. When the IP4000 was analysed as a function of the best score on any of the three test days after altitude training there was a 4% improvement that was not reflected in a corresponding change in VO2max or Hb mass. RBC creatine concentration was significantly reduced after altitude training, suggesting a decrease in the average age of the RBC population. However, measurement of reticulocyte number and serum concentrations of erythropoietin, haptoglobin and bilirubin before and after altitude provided no evidence of increased RBC turnover. The data suggest that for these elite cyclists any benefit of altitude training was not from changes in VO2max or Hb mass, although this does not exclude the possibility of improved anaerobic capacity.

Adult↗
PubMed1998

Managerialism, information technology and health reform in New Zealand.

Recent health reform in New Zealand has transformed public hospitals and related health services into Crown Health Enterprises (CHEs), which have a statutory objective to operate as successful and efficient businesses. Examines managerialist interpretations of a proposed executive information system (EIS) at one CHE. Arguably, the use of computerized information systems signals managerial competence and rationality, and there was an implicit assumption among senior CHE managers that "business-like" and "efficient" management required the use of information technology. In the end, in the context of continuing organizational restructuring, the EIS was never implemented.

Benchmarking↗
PubMed1997

Decrease of very late activation antigen-4 and CD36 on reticulocytes in sickle cell patients treated with hydroxyurea.

Sickle cell disease (SCD) is characterized by repeated vaso-occlusive events, which result in substantial morbidity. Abnormal adhesion of sickle red blood cells (RBC) to the vascular endothelium is postulated to play a role in the pathogenesis of vaso-occlusion. Two adhesion receptors, very late activation antigen-4 (VLA-4) and CD36, are found in unusually high numbers on sickle cell reticulocytes and do mediate adhesion of sickle RBC to endothelium. Hydroxyurea (HU) therapy results in fewer vaso-occlusive episodes, and we postulated that HU-related modulation of VLA-4 and CD36 receptors may contribute to its clinical benefit. Using flow cytometry, eight patients were followed from the onset of HU treatment through a mean treatment length of 200 +/- 49 days. Mean corpuscular volume and percent fetal hemoglobin (Hb F) increased from 87% +/- 6% to 98% +/- 9% and 6.6% +/- 3.9% to 12.7% +/- 5.6%, respectively. The percentage of reticulocytes expressing VLA-4 decreased from 29.0% +/- 5.9% to 14.9% +/- 2.3% (P = .0003). Two thirds of the total decrease in VLA-4 expression occurred after 10 weeks of HU and plateaued by 20 weeks. Changes in VLA-4 expression occurred before substantial increases in Hb F. The percentage of reticulocytes expressing CD36 decreased from 55.3% +/- 6.4% to 42.6% (P = .0046). Changes in adhesion receptor expression were not caused by a decrease in reticulocytosis with HU therapy. This report is the first to associate a decrease in adhesion receptor expression with a therapy known to reduce the clinical severity of SCD.

Adolescent↗
PubMed1997

Muscle phosphocreatine repletion following single and repeated short sprint efforts.

Phosphocreatine (PCr) repletion following either single (1x6 s, n=7) or repeated (5x6 s, departing every 30 s, n=8) maximal short sprint cycling efforts was measured in separate groups of trained subjects. Muscle biopsies (vastus lateralis) were taken pre-exercise before warming up, and then at 10 s, 30 s and 3 min post-exercise. After the 1 x 6 s sprint PCr concentration was respectively, 55% (10 s; P<0.01), 69% (30 s; P<0.01) and 90% (3 min; NS) of the pre-exercise value (mean+/-SD) (81.1+/-7.4 mmol x kg(-1) DM), whereas after the 5x6 s sprints, PCr concentration was, respectively, 27% (10 s; P<0.01), 45% (30 s; P<0.01) and 84% (3 min; P<0.01) of the pre-exercise value (77.1+/-4.9 mmol x kg(-1) DM). PCr concentration was correlated with muscle lactate at 30 s (r=-0.82; P<0.05) and 3 min of recovery (r=-0.94; P<0.01) for the 1x6 s sprint, but not for the 5x6 s sprints. The extent of PCr repletion was significantly greater after the 5x6 s sprints than the 1x6 s sprint between both 10 s and 30 s and 30 s and 3 min, despite lower PCr levels at 10 s, 30 s and 3 min following the 5x6 s sprints. Full repletion of PCr is likely to take longer after repeated sprints than single short sprints because of a greater degree of PCr depletion, such that replenishment must commence from lower PCr levels rather than because of slower rates of repletion.

Adult↗