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Biomedical subjects

M G Nelson

Publications and source records attributed to M G Nelson.

At least 19 recordsLinked to original sources
PubMed2000

Assessment of perfusion toward the aortic valve using the new dispersion aortic cannula during coronary artery bypass surgery.

When there is an echocardiographic diagnosis of severe mobile atherosclerotic plaque in the aortic arch or descending aorta, perfusion toward the aortic arch during cardiopulmonary bypass may create a high risk of embolic neurologic injury. Other perfusion methods, such as cannulation of the femoral or axillary arteries, are not always possible, due to atherosclerosis. The ascending aorta may be an alternative site for perfusion, since it is less frequently diseased. We assessed a new technique of perfusion toward the aortic valve using a new cannula designed for this purpose (Dispersion aortic cannula). Our study included 100 consecutive patients, 72 men and 28 women, with an average age of 68 +/- 1.0 years (range, 39-89 years). There were no complications related to insertion of the cannula or perfusion. The ascending aorta could be cross-clamped and side-clamped without perfusion problems. Three deaths occurred; none was related to the cannulation technique. No intra-operative stroke occurred. Two patients suffered neurologic events, one on day 1 and the other on day 6; both had been fully alert after surgery. Perfusion toward the aortic valve appears to be safe and hemodynamically effective. This cannulation technique appears to be an acceptable alternative to present methods. Comparative studies will be needed to determine whether this alternative technique is effective in patients with severe aortic arch disease.

Adult↗
PubMed1998

A new structural class of proteasome inhibitors that prevent NF-kappa B activation.

The multicatalytic proteinase or proteasome is a highly conserved cellular structure that is responsible for the ATP-dependent proteolysis of many proteins involved in important regulatory cellular processes. We have identified a novel class of inhibitors of the chymotrypsin-like proteolytic activity of the 20S proteasome that exhibit IC50 values ranging from 0.1 to 0.5 microgram/mL (0.1 to 1 microM). In cell proliferation assays, these compounds inhibit growth with an IC50 ranging from 5 to 10 micrograms/mL (10-20 microM). A representative member of this class of inhibitors was tested in other biological assays. CVT-634 (5-methoxy-1-indanone-3-acetyl-leu-D-leu-1-indanylamide) prevented lipopolysaccharide (LPS), tumor necrosis factor (TNF)-, and phorbol ester-induced activation of nuclear factor kappa B (NF-kappa B) in vitro by preventing signal-induced degradation of I kappa B-alpha. In these studies, the I kappa B-alpha that accumulated was hyperphosphorylated, indicating that CVT-634 did not inhibit I kappa B-alpha kinase, the enzyme responsible for signal-induced phosphorylation of I kappa B-alpha. In vivo studies indicated that CVT-634 prevented LPS-induced TNF synthesis in a murine macrophage cell line. In addition, in mice pretreated with CVT-634 at 25 and 50 mg/kg and subsequently treated with LPS, serum TNF levels were significantly lower (225 +/- 59 and 83 +/- 41 pg/mL, respectively) than in those mice that were treated only with LPS (865 +/- 282 pg/mL). These studies suggest that specific inhibition of the chymotrypsin-like activity of the proteasome is sufficient to prevent signal-induced NF-kappa B activation and that the proteasome is a novel target for the identification of agents that may be useful in the treatment of diseases whose etiology is dependent upon the activation of NF-kappa B.

Adenosine Triphosphatases↗
PubMed1997

Regioselective effect of zwitterionic DNA substitutions on DNA alkylation: evidence for a strong side chain orientational preference.

The incorporation of zwitterionic residues (5-substituted omega-aminoalkyl-2'-deoxypyrimidines) into DNA has been reported to bend DNA as measured by aberrant gel mobility [Strauss et al. (1996) Proc. Natl. Acad. Sci. U.S.A. 93, 9515-9520]. Herein we report that DNA methylation by N-methyl-N-nitrosourea at N7-guanine is regioselectively inhibited by point substitutions of the zwitterionic residues 5-(6-aminohexyl)-2'-deoxycytidine, 5-(6-aminohexyl)-2'-deoxyuridine, or 5-(3-aminopropyl)-2'-deoxyuridine. No inhibition is observed for DNA methylation by dimethyl sulfate. On the basis of inhibition patterns for methylation with the different zwitterionic substitutions and the different length tethers, the omega-aminoalkyl side chains prefer to adopt a conformation that points them toward the 3'-base. Molecular modeling grid searches, coupled with energy minimizations, and simulated annealing molecular dynamics studies indicate that unfavorable steric interactions with the 5'-base and backbone, as well as stabilizing electrostatic interactions with electronegative atoms on the 3'-side, are responsible for the observed conformational preference. No evidence for association of the cationic side chain with the phosphate backbone is observed. The observed bending of DNA induced by the tethered ammonium ions may simply arise from their localization in the major groove.

Circular Dichroism↗
PubMed1996

DNA bending by hexamethylene-tethered ammonium ions.

DNA is bent when complexed with certain proteins. We are exploring the hypothesis that asymmetric neutralization of phosphate charges will cause the DNA double helix to collapse toward the neutralized face. We have previously shown that DNA spontaneously bends toward one face of the double helix when it is partially substituted with neutral methylphosphonate linkages. We have now synthesized DNA duplexes in which cations are tethered by hexamethylene chains near specific phosphates. Electrophoretic phasing experiments demonstrate that tethering six ammonium ions on one helical face causes DNA to bend by approximately 5 degrees toward that face, in qualitative agreement with predictions. Ion pairing between tethered cations and DNA phosphates provides a new model for simulating the electrostatic consequences of phosphate neutralization by proteins.

Base Sequence↗
PubMed1994

Computed tomographic diagnosis of acute blunt pancreatic transection.

Pancreatic injuries secondary to blunt trauma are challenging to diagnose. In many cases, the diagnosis is missed or delayed due to the subtle symptoms and signs of pancreatic injury. Blunt pancreatic injuries may evolve over a period of time and can be a source of extensive morbidity and mortality. Most radiologic and laboratory studies have been notoriously nonspecific in diagnosing pancreatic injuries. This article discusses three patients we treated with pancreatic transection secondary to blunt trauma, who underwent computed tomography (CT) of the abdomen on admission. The pertinent CT findings and utility of CT as a diagnostic tool in these three cases of blunt pancreatic injuries are reviewed. Abdominal CT scanning can accurately identify pancreatic injuries secondary to blunt trauma, allowing expeditious surgical intervention. A high index of suspicion for pancreatic injury combined with careful interpretation of abdominal CT scans can provide valuable information about pancreatic injury during the initial trauma assessment.

Accidents, Occupational↗
PubMed1988

Red cell pyrimidine 5' nucleotidase deficiency: determination of nucleotidase activity and nucleotide content using HPLC.

The hereditary deficiency of erythrocyte pyrimidine 5' nucleotidase has been investigated using an HPLC anion-exchange procedure designed to measure both red cell nucleotide content and enzymic activity. Red cell nucleotide profiles were determined using a low pH phosphate buffer salt-gradient system in 20 min, whereas a low pH buffer alone permitted the determination of enzymic activity with each of six different nucleotide substrates in less than 4 min. Both the red cell nucleotide profiles and the enzymic activity of haemolysates from two affected brothers and their children agreed well with previously published values. This unified approach should prove useful for detailed studies of deficiencies involving isoenzymes of pyrimidine nucleotidase.

5'-Nucleotidase↗
PubMed1981

Determination of the oxygen dissociation curve and P50 of whole blood. An evaluation of the Hem-O-Scan and instrumentation of laboratory systems.

The Travenol Hem-O-Scan and the Instrumentation Laboratory (IL) system for determination of the oxygen dissociation curve and P50 values have been evaluated. Using the Hem-O-Scan, an oxygen dissociation curve and P50 value may be obtained on 2 microliter of blood in 40 min, though the pH is not measured. In the IL system, approximately 3 ml of blood is required to establish four points on the oxygen dissociation curve in 80 min, and pH data are available. Both systems give reproducible results for P50, giving standard deviations of 0.786 mm Hg for the Hem-O-Scan and 0.949 mm Hg for the IL system, compared with 1.740 mm Hg for the manual system. Good agreement was found between the manual method and Hem-O-Scan (t = 0.363, degrees of freedom = 19, 0.8 greater than P greater than 0.7; r = 0.892, P less than 0.001). There was also satisfactory agreement between the IL system and the Hem-O-Scan (t = 0.370, degrees of freedom = 20, 0.8 greater than P greater than 0.7; r = 0.760, P less than 0.001). P50 values obtained by the manual and by both automated technics agree well with published values.

Adult↗
PubMed1980

Processing haematological data on a dedicated computer.

A system of processing the laboratory data of a busy haematology department serving a teaching group of hospitals and the general practitioners of the district is described. The system, which has been in routine use for over two years, is based on a dedicated CTL8030 computer sited in the laboratory utilising Lynwood visual display units (VDUs) for both input and access to the data files. Data from the Coulter 'S' is fed by an interface to the computer and to other data handling modules. Manual test results are entered via VDUs, mainly by laboratory staff who also validate all data. Access is available to all data for answering telephone requests. Data are retained on the disc file for 48 hours only, and cumulative reporting was not planned into the system as deliberate policy. Quality control of the Coulter 'S' output is maintained both throughout the day and retrospectively at the end of each working day using both whole blood patient blood transfusion profiles, a record of blood and product usage, worksheets, quality control information, end-of-day listing in alphabetical order plus statistical information for administrative purposes. Since its introduction the system has been remarkably free from breakdown as a result of hardware failure. A number of fail safe/fallbacks have been included in the system.

Blood Cell Count↗
PubMed1979

Intralaboratory quality control of hematology. Comparison of two systems.

Two systems for quality control have been compared, viz., the whole-blood control preparation method and the algorithm method using the geometric moving average XB and a new estimator Y. The system involving whole-blood controls has the advantage of simplicity of operation, but the economic cost of commercial preparations is often high. The algorith system has the advantage that results of all the test samples are used in the calculation; to some extent, this provides a buffer against random variation. The number of count-outs in a given channel is related to the precision of the channel, which in turn is a function of the number of determinations and calculations required for that result. An error of around 1% is introduced into the result each time a calculation is performed. A successful quality control scheme should contain elements of both control preparation and algorithm methods.

Erythrocyte Count↗
PubMed1972

An evaluation of the Celloscope 401 electronic blood cell counter.

For counting erythrocytes the instrument was precise, with a mean coefficient of variation of 1.21%. Erythrocyte counts showed close agreement with results obtained on a Coulter A electronic counter of proven accuracy. When the Celloscope 401 was modified by the manufacturers to eliminate electrical interference from other laboratory equipment, satisfactory precision and accuracy for white cell counting was obtained. Using cetrimide diluent the coefficient of variation was 1.6% but when using saponin/saline diluent the coefficient of variation was 3.5%. For leucocyte counting there was close agreement between duplicate tests performed on the Celloscope 401 and the Coulter S. The instrument was capable of satisfactory precision and accuracy in platelet counting, provided that the sedimentation method was used to obtain a platelet-rich plasma. The best results were obtained if a two-step dilution was carried out with a first dilution in 10% EDTA and a second in 2.5 mM cocaine in water. Using this method the precision study indicated a coefficient of variation of 3.11%. Close agreement was obtained between platelet counts on the Celloscope 401 when compared with the results obtained either by phase-contrast microscopy or using another electronic counter. Allowing for predilution and duplicate counts on each sample, the rate of throughput was approximately 32 samples per hour. Throughout the test period, the instrument remained electronically and mechanically stable.

Blood Cell Count↗
PubMed1972

Data processing in haematology.

The output from a Coulter model S is captured by a specially designed silent interface which visualizes the results, automatically prints the data on a continuous paper roll and transmits the information to a card punch located in a data processing room. Further requested test data and patient identification data are subsequently added manually to the punch card. The completed deck of cards is used in an off-line batch mode on a dedicated laboratory computer to format report documents, produce ward listings, and quality control information. A punch card off-line method is also described for blood group and related data.

Autoanalysis↗
PubMed1970

An evaluation of the Fisher Hem-Alyzer.

The Fisher Hem-Alyzer is a multitest sequential discrete analyser with automatic printout of digitized results on paper tape. The instrument is well designed, soundly constructed, and reliable in routine use. Cross contamination from the sampler probe or between the cuvettes is minimal. Accuracy and precision are both highly satisfactory. Although the standard rate of throughput is 32 specimens per hour the instrument can be used at irregular intervals to analyse smaller batches or even individual specimens. In a routine daily service the Hem-Alyzer was capable of handling a workload of 200 specimens per day, requiring three hours of laboratory technician time. The Hem-Alyzer produces only three parameters. By not determining the packed cell volume it is not possible to incorporate the derived indices (MCV and MCHC) into the system and this, in the long term, is bound to be a disadvantage.

Autoanalysis↗