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Biomedical subjects

D S Reid

Publications and source records attributed to D S Reid.

At least 19 recordsLinked to original sources
PubMed1992

Characterization of primitive hematopoietic cells in normal human peripheral blood.

The total number of clonogenic cells present in 5-week-old long-term cultures (LTC) initiated by seeding normal human marrow cells on competent adherent cell feeder layers allows for the quantitation of a more primitive hematopoietic input precursor cell type referred to as an LTC-initiating cell (LTC-IC). Previous studies have suggested that LTC-IC also circulate because production of clonogenic cells continues for many weeks when cells from the light-density (< 1.077 g/mL), T-cell-depleted fraction of normal blood are maintained on irradiated, marrow-derived feeder layers in LTC medium. We now show that the number of clonogenic cells present in such reconstructed LTC after 5 weeks is linearly related to the input number of peripheral blood (PB) cells over a wide range of cell concentrations, thereby permitting the quantitation of circulating LTC-IC by limiting dilution analysis. Using this approach, we have found the concentration of LTC-IC in the circulation of normal adults to be 2.9 +/- 0.5/mL. This is approximately 75-fold lower than the concentration of circulating clonogenic cells (ie, burst-forming units-erythroid plus colony-forming units [CFU] granulocyte-macrophage plus CFU-granulocyte, erythroid, monocyte, megakaryocyte) and represents a frequency of LTC-IC relative to all nucleated cells that is approximately 100-fold lower than that measured in normal marrow aspirate samples. Characterization studies showed most circulating LTC-IC to be small (low forward light scatter and side scatter), CD34+, Rh-123dull, HLA-DR-, and 4-hydroperoxycyclophosphamide-resistant cells, with differentiative and proliferative potentialities indistinguishable from LTC-IC in normal marrow. Isolation of the light-density, T-cell-depleted, CD34+, and either HLA-DR(low) or Rh-123(dull) fraction of normal blood yielded a highly enriched population of cells that were 0.5% to 1% LTC-IC (approximately 1,500-fold enriched beyond the light-density, T-cell-depletion step), a purity comparable to the most enriched populations of human marrow LTC-IC reported to date. However, purification of PB LTC-IC on the basis of these properties did not allow them to be physically separated from a substantial proportion (> 30%) of the clonogenic cells in the same samples, in contrast to previous findings for LTC-IC and clonogenic cells in marrow. These studies show the presence in the blood of normal adults of a relatively small but readily detectable population of functionally defined, primitive hematopoietic cells that share properties with marrow LTC-IC, a cell type thought to have in vivo reconstituting potential.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1992

Rapid decline of chronic myeloid leukemic cells in long-term culture due to a defect at the leukemic stem cell level.

In this report we describe a quantitative in vitro assay for the most primitive type of leukemic precursors yet defined in patients with chronic myeloid leukemia (CML). This assay is based on the recently described "long-term culture-initiating cell" (LTC-IC) assay for primitive normal human hematopoietic cells. Such cells, when cocultured with competent fibroblast feeder layers, give rise after a minimum of 5 weeks to multiple single and multilineage clonogenic progenitors detectable in secondary semisolid assay cultures. Similar cultures initiated by seeding a highly enriched source of leukemic cells from patients onto normal feeders showed the clonogenic cell output after 5 weeks to be linearly related to the input innoculum over a wide range down to limiting numbers of input cells, thus allowing absolute frequencies of leukemic LTC-ICs to be determined using standard limiting dilution analysis techniques. Leukemic LTC-IC concentrations in CML marrow were found to be decreased, on average to less than 10% of the normal LTC-IC concentration in normal marrow, but were greatly increased (up to greater than 10(5) times) in CML blood. Assessment of the number of clonogenic cells produced per leukemic LTC-IC by comparison to normal blood or marrow LTC-IC values showed this function to be unchanged in leukemic LTC-ICs [i.e., 3.1 +/- 0.4 clonogenic cells per CML LTC-IC (mean +/- SEM, n = 6) versus 3.7 +/- 1.2 (n = 3) and 4.3 +/- 0.4 (n = 5), respectively, for normal blood and marrow LTC-ICs]. In contrast, leukemic LTC-IC maintenance in LTC proved to be highly defective by comparison to normal LTC-IC of either blood or marrow origin. Thus, when cells from primary LTC were subcultured into secondary LTC-IC assays, leukemic LTC-IC rapidly declined (greater than 30-fold) within the first 10 days of culture, whereas normal LTC-IC numbers remained unchanged during this period. These findings illustrate how self-maintenance and differentiation events in primitive human hematopoietic cells can be differentially modulated by an oncogenic process and provide a framework for further studies of their manipulation, analysis, and therapeutic exploitation.

Bone Marrow↗
PubMed1992

Septal rupture after myocardial infarction: is very early surgery really worthwhile?

Despite numerous publications, mostly with small patient populations, the management of post-infarct septal rupture is still not well defined. Although urgent surgery appears to be the therapy of choice it is still unclear whether surgery very early after septal rupture in patients with severe haemodynamic compromise salvages a significant number of patients. In this paper we present the data from a large population of consecutive patients with post-infarct septal rupture from one cardiac centre. From 1980 through 1989, 108 patients with post-infarct septal rupture were seen at this Regional centre of whom 81 had operative repair; 43 (53%) of these survived the early postoperative period. Of 32 patients with cardiogenic shock who had surgery, early operative mortality in those operated on within 48 h of rupture was 90% (18/20) compared with 33% (4/12) in those operated on later (P less than 0.001). All survivors with pre-operative shock had intra-aortic balloon counter-pulsation before operation. Concomitant coronary artery bypass grafting was not associated with improved survival in our patients. Three patients survived long-term without operation. Analysis of population statistics suggest that approximately 270 patients with post-infarction septal rupture were not transferred from peripheral hospitals to the Regional Cardiothoracic Centre for assessment during this decade.

Aged↗
PubMed1992

Incessant atrial tachycardia accelerated by pregnancy.

A 24 year old patient presented with incessant atrial tachycardia during the course of a twin pregnancy. Medical treatment slowed the ventricular response without restoring sinus rhythm. During labour the tachycardia spontaneously reverted to sinus rhythm. Subsequently the same arrhythmia was documented with a slower ventricular response than during pregnancy.

Adult↗
PubMed1992

The occurrence of early sudden coronary artery occlusion following angioplasty may be predicted from the clinical characteristics of the patients and their coronary lesion morphology.

The aim of this study was to assess whether the incidence of early occlusion following angioplasty was greater among patients with unstable angina and whether the coronary lesions prone to early occlusion could be predicted from their angiographic appearance. Seventy-seven patients who had had a first angioplasty of a native vessel for stable or unstable angina in one twelve month period were included. The angiographic appearances of the angioplastied lesions were classified as either Type 1, which were smooth and unlikely to have thrombus or intimal rupture, or Type 2, which were irregular due to thrombus or intimal rupture. The lesion classification was compared to the patients' clinical features, i.e. stable or unstable angina, and the outcome of the angioplasty. Type 2 lesions occurred in 25% of patients with stable angina but 49% of patients with unstable angina (p less than 0.05). Early sudden occlusion of the angioplastied vessel occurred in 24% of patients with unstable angina but in only 3% of patients with stable angina (p less than 0.05) and in 6% of Type 1 lesions compared with 24% of Type 2 lesions (p less than 0.05). Thus it is possible to identify the clinical characteristics and angiographic appearances of those patients undergoing angioplasty who are most likely to experience early vessel occlusion.

Angina Pectoris↗
PubMed1991

Phase volume measurements using magnetic resonance imaging.

The phase distribution of components in both model and actual food systems has been quantified using Magnetic Resonance Imaging. We present measurements of effective moisture diffusivities, vertical mass distributions in foams, and crystallization of water and lipid components. The interpretation of this information allows one to quantify the interactions of various components and structural features within a sample. These measurements are made noninvasively and nondestructively and can be repeated over time to obtain information on the dynamics of the system.

Chemical Phenomena↗
PubMed1991

Ionic diffusion in frozen starch gels.

Quality changes in food frozen by different conditions and at different storage temperatures were demonstrated using a model system. A frozen starch gel represents a frozen food matrix, and ions in the external medium represent the reactant molecules. We determined the effective diffusion rates of Zn+2 ions into frozen starch gel cylinders that were frozen at different freezing rates. The diffusion was performed at -8 degrees and -15 degrees C. The amounts of ion diffused were determined by atomic absorption, whilst the structure of the frozen samples could be simultaneously determined by scanning electron microscopy. The effective diffusion rates were found to correlate with the amount of unfrozen portion of the samples. This suggests that ions move mainly through the unfrozen portion around the ice crystals. Fast- and slow-frozen samples exhibited significantly different effective diffusion rates at -15 degrees C, which might be due to differences in size and orientation of ice crystals. Zn+2 ions moved slower at -15 degrees C than at -8 degrees C.

Crystallization↗
PubMed1991

Studies of reaction kinetics in relation to the Tg' of polymers in frozen model systems.

The rates of diffusion-controlled processes in a frozen system can be influenced by the presence of glassy states. One characteristic of cryostabilization by this mechanism is a change in the temperature dependence of reaction rates at the Tg' of the system. The cryostabilization behavior of solutes such as maltodextrin, carboxymethylcellulose (CMC), and sucrose was studied. Three different model reaction systems (enzyme hydrolysis, protein aggregation, and non-enzymatic oxidation) were used. Maltodextrin had a consistent pattern of cryostabilization behavior at temperatures ranging from -3 degrees C to -20 degrees C for all three model systems. Significant retardation effects were evident in the temperature range corresponding to its glassy states. Sucrose did not show a stabilizing effect in the non-proteinaceous model system (the non-enzymatic oxidation reaction). This could partly be due to the absence of the glassy state, since the storage temperatures were above its Tg'. However, in the protein aggregation model system, sucrose was an excellent stabilizer in protecting actomyosin from aggregation. This may be explained by a "solute exclusion" mechanism. CMC did not show any stabilizing effect in the protein aggregation and non-enzymatic oxidation model systems studied, even though it has a Tg' as high as that of maltodextrin. These results demonstrated that although the presence of a glassy state may well have a retarding effect on the rates of diffusion processes, just knowing the Tg' of a polymer is not sufficient for prediction of its stabilization effect in a frozen system.

Actomyosin↗
PubMed1991

Effect of solute on the nucleation and propagation of ice.

Using the emulsion technique, we have studied nucleation of ice in aqueous solutions containing silver iodide or Pseudomonas syringae. Using a Differential Scanning Calorimeter (DSC), we determined characteristic temperatures of nucleation, and also rates of nucleation at selected temperatures. The freezing point depression induced by added solute is linearly related to the lowering of both homogeneous and heterogeneous nucleation temperature. Nucleation kinetics depend on a fifth power function of the temperature. Solute is found to affect the parameters of this relationship in different ways, dependent upon the nature of the catalytic site for ice nucleation. We have also studied the effect of composition on the linear propagation velocity (LPV) of ice in undercooled solutions contained in a U-tube. We have determined velocities in a range of concentrations of sugar solution at the same undercooling, and also as a function of undercooling. The role of added polymer has also been investigated. It is affected by the sugar concentration.

Calorimetry, Differential Scanning↗
PubMed1991

Salmonella: a rare cause of subacute effusive-constrictive pericarditis.

A 36 year old woman had emergency pericardectomy because of subacute effusive-constrictive pericarditis. The pericardial fluid and tissue culture showed that this was caused by infection with Salmonella enteritidis. Cardiac involvement with salmonella does not usually present in such an aggressive manner and it has not previously been reported to cause this rare type of cardiac constriction.

Acute Disease↗
PubMed1991

Melanoma metastatic to breast.

A patient presented with an unusual case of a breast mass. History and meticulous physical examination led to the diagnosis of metastatic melanoma, which was confirmed by biopsy. The differential diagnosis of metastasis to breast is discussed.

Adult↗
PubMed1990

Reduction in ST segment elevation after thrombolysis predicts either coronary reperfusion or preservation of left ventricular function.

The usefulness of a reduction in ST segment elevation to predict coronary reperfusion in myocardial infarction remains uncertain. ST segment changes and angiographic findings were compared in 45 patients soon after thrombolysis. The percentage ST segment change 3 hours after treatment (in the lead showing the greatest initial ST elevation) was compared with the TIMI perfusion grade (thrombolysis in myocardial infarction trial) obtained between 90 minutes and 3 hours after treatment. Global ejection fraction and regional wall motion were assessed by cineventriculography (11 (5) days (mean (SD))) and by gated blood pool imaging (44 (11) days). Prediction of coronary patency by a reduction of greater than 25% in ST segment elevation 3 hours after thrombolytic treatment had a sensitivity of 97% but a specificity of only 43%. Where the ST segment elevation was reduced by greater than 25% the global ejection fraction was well maintained whether or not the infarct vessel was patent. In patients with a reduction of less than 25% in ST elevation, the ejection fraction was significantly lower and regional wall motion abnormality more severe. Reduction in ST elevation of greater than 25% within 3 hours of thrombolysis indicates either a patent infarct artery or preservation of left ventricular function. When the ST segment elevation does not fall by greater than 25% persistent coronary occlusion is likely (predictive accuracy 86%) and is associated with a lower ejection fraction. These patients may benefit from further treatment or additional interventions.

Adult↗
PubMed1988

Coupling of redox indicator dyes into an enzymatic reaction cycle.

The spectral properties of ten redox indicator dyes were evaluated with the aim of finding the optimal choice for coupling to enzymatic reactions with high sensitivity for the production of the reduced form. Eight of the dyes were selected for coupling into a reaction cycle formed by yeast alcohol dehydrogenase with substrates ethanol and nicotinamide adenine dinucleotide (NAD+) and diaphorase with substrates reduced nicotinamide adenine dinucleotide (NADH, produced by the prior reaction) and the oxidized form of the respective dye. Two of the dyes exhibited decreased absorption on reduction, whereas all (eight) tetrazolium dyes increased in their absorption substantially upon reduction. Bis-tetrazolium dyes had a significantly higher molar extinction coefficient (up to 23,000 M-1.cm-1) than mono-tetrazolium dyes (down to 8000 M-1.cm-1). Kinetically, most dyes could be reduced with NADH (and diaphorase), but the rate of reduction varied considerably among the dyes with nitroblue tetrazolium (NBT) and tetranitroblue tetrazolium (TNBT) being the fastest. Therefore, NBT and TNBT seem to be the most suitable for fast response.

Alcohol Dehydrogenase↗
PubMed1987

Prevention of tolerance to nitroglycerin patches by overnight removal.

This investigation assesses the extent of tolerance development with nitroglycerin patches and whether tolerance might be prevented by overnight patch removal. On commencing therapy, active patches significantly prolonged exercise time (3.5 hours after patch application) in comparison with placebo, with an accompanying reduction in ST-segment depression at maximal common workload. Patients then received continuous or 12-hour-daily intermittent patch therapy, in a double-blind fashion, for 7 days. Exercise testing was repeated before and after active patch application, on the eighth day of each treatment phase. During continuous therapy, beneficial effects on exercise time and ST depression were abolished. By contrast, during intermittent therapy, prolongation of exercise time and reduction in ST-segment depression still occurred, on testing 3.5 hours after active patch application. These results confirm previous studies showing a high degree of tolerance during continuous therapy with nitroglycerin patches and suggest that tolerance can be prevented by 12-hour-daily intermittent therapy.

Administration, Cutaneous↗
PubMed1987

Flecainide--an intravenous infusion regimen.

An intravenous infusion regimen for flecainide was studied in 12 patients. Therapeutic drug levels were rapidly established and maintained throughout the 48-h infusion period. Two patients were withdrawn because of possible drug related problems, but in general the regimen seemed both effective and well tolerated.

Aged↗
PubMed1987

Gravitational and magnetic activation methods applied to cultured cells (LK 35.2).

Monoclonal antibody 10.2-16 is directed toward the mouse class II major histocompatibility complex gene product 1-Ak expressed on the cell line LK35.2. Instead of activating cells by fluorophor we used (acrylamide-coated) heavy and magnetic microspheres of 0.6 micron in radius. These microspheres are chemically coupled (carbodiimide method) with the antibody toward the surface antigen. The cells are observed through a microscope with horizontal alignment, as they sediment in a (temperature controlled) tube with square cross-section. Stokes Law allows the determination of the density of cells (first alone) using viscosity and density of Dulbecco's modified Eagle's Medium together with the observed mean sedimentation velocity (66 microns/min) and a mean diameter of 10 microns. We found a density of 1.0558 +/- 0.0028 g/cm3 at 10 degrees C. Independently, thinly coated, heavy (and magnetizable) microspheres with the cited antibody are attached to cells and observed likewise. The increased sedimentation velocity permits us to show that the cells were fully covered with microspheres (290 per cell). A magnetic field gradient opposing gravity moved these cells against gravity with two different mean velocities, 340 microns/min and 850 microns/min. The higher velocity resulted in 290 particles per cell, the lower one in 130 particles per cell. The limits for the expansion of this method to smaller particle sizes (down to 10 nm) are evaluated.

Antibodies, Monoclonal↗
PubMed1987

Effect of aryl 4-guanidinobenzoates on the acrosin activity of human spermatozoa.

Certain aryl 4-guanidinobenzoates (AGs; inhibitors of proteinases, including the sperm enzyme acrosin) have been shown to be more potent vaginal contraceptives in rabbits and less toxic than nonoxynol-9, the active ingredient of most marketed vaginal contraceptive formulations. To determine if these AGs can contact sperm and inhibit acrosin when mixed with the entire human ejaculate for a short period of time (roughly imitating clinical conditions), the inhibitors were added to semen at various concentrations for 2 min, after which the seminal plasma and unbound inhibitor were removed from the sperm by Ficoll centrifugation. Subsequently, the total arginine amidolytic activity of the spermatozoa was determined spectrophotometrically after a combined treatment that resulted in extraction, proacrosin activation, and reaction with substrate. Dose-response curves were prepared. All AGs studied were effective inhibitors of the amidolytic activity under these conditions, with ED50 values (the dose levels at which half of the acrosin associated with 10(6) sperm is inhibited) ranging from 10(-5) to 10(-7) M. To determine the effect on the proteolytic activity of individual spermatozoa, the experiment was repeated with 4'-acetamidophenyl 4-guanidinobenzoate (AGB), and the protease released from the sperm was measured by the gelatin-plate assay. The inhibition results were similar to those obtained by extraction of the spermatozoa and measurement of amidolytic activity. Thus, when mixed with the human ejaculate, AGs interact rapidly with spermatozoa to inhibit both their arginine amidolytic and proteolytic activity (probably due primarily or only to inhibition of acrosin) and remain bound even after removal of the seminal plasma. These data encourage further study of the compounds for contraceptive purposes.

Acrosin↗