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Biomedical subjects

W Simon

Publications and source records attributed to W Simon.

At least 55 records · Page 3Linked to original sources

Ion-selective membrane electrodes for clinical use.

We review ion-selective solvent polymeric membrane electrodes for clinical use. The particular requirements that the clinical application set on the membrane are discussed in terms of selectivity, stability, lifetime, and response time. The performance of currently available electrodes is reviewed, with consideration of actual problems that arise in clinical practice.

Bicarbonates

Variables influencing the timing of marrow transplantation in patients with chronic myelogenous leukemia.

The prognosis for patients with chronic myelogenous leukemia (CML) has improved only for patients who can receive marrow transplantation from a histocompatible sibling. The timing of the marrow transplant is made difficult by the high peritransplant mortality of 20% to 35% and a group of patients with a prolonged chronic phase of CML, which can be identified on the basis of prognostic indexes (age, percent blood myeloblasts, spleen size, and platelet count). We have developed a mathematic model and computer program that consider age, prognostic index, and projected survival rate by transplantation to balance the risk of peritransplant mortality against the risk of delaying the transplantation of patients with Philadelphia chromosome-positive CML. The computation assesses the risk of delaying transplantation; it does not offer the option of avoiding transplantation, since long-term survival ultimately requires transplantation. Three prognostic groups were considered as described by Sokal and co-workers (Blood 63:789, 1984) (I, best; II, intermediate; III, worst prognosis). The computation used the projected survival rates of transplantation from the Seattle experience and from the International Bone Marrow Transplant Registry. As an example of the model's utility, we have determined the ratio of the calculated life expectancy to the normal life expectancy for hypothetical patients up to 50 years of age in each of the three prognostic categories. A value of 20% is used for patients who successfully receive transplants after the onset of the accelerated phase. The analysis allows assessment of the risk of delaying transplantation for a finite time in patients with CML. The importance of the method rests in its consideration of multiple variables, including the peritransplant mortality, transplant projected survival before and upon entering the accelerated phase, age, prognostic group, and other risk factors. The program permits a change in these parameters as new information or advances in treatment occur. This analysis does not replace the diagnostic deliberations of the clinician. Rather, it provides a numeric framework for prognosis based on the currently available data. The physician in conjunction with the patient, not the algorithm, makes the decisions of whether and when to transplant.

Age Factors

Cell counts in cerebral cortex of an autistic patient.

Numbers of neurons and glia were counted in the cerebral cortex of one well-documented case of autism and two age- and sex-matched controls. Areas in which cell counts were made were primary auditory cortex, Broca's speech area, and auditory association cortex. No consistent differences in cell density were found between the brains of the autistic patient and the control patients.

Adolescent

Multicomponent analysis of amino acid transport in human lymphocytes. Diminished L-system transport in chronic leukemic B lymphocytes.

We have examined the amino acid transport in B cell chronic lymphocytic leukemia and compared it with the amino acid transport in isolated B lymphocytes from human blood and tonsils. L-system transport was measured with 2-amino-2-carboxy-bicyclo (2,2,1)-heptane, which is a synthetic amino acid whose transport is limited to the L-system. Amino acid uptake was subjected to a multicomponent analysis that partitioned the total uptake into the saturable carrier-mediated transport system and the uptake by diffusion. The maximal velocity of L-system transport in chronic lymphocytic leukemia cells, 81 mumol/1 cell water per min, was less than 10% that of blood B lymphocytes, which was 1,029 mumol/1 cell water per min. The uptake of 2-amino-2-carboxy-bicyclo (2,2,1)-heptane by tonsillar B cells, by a B lymphocyte cell line, and by blood T-lymphocytes was also 10-fold greater than that observed in chronic lymphocytic leukemic cells. Similarly, the L-system uptake of leucine and phenylalanine, which are naturally occurring amino acids usually transported primarily by the L-system, was reduced in chronic lymphocytic leukemic B cells to 15 and 10% of normal B cells, respectively. Total leucine uptake by chronic lymphocytic leukemic cells, however, was sustained at 30% of that expected because of transport via an alternative transport system. The A- or ASC-systems, the other major amino acid transport pathways, were not defective in chronic lymphocytic leukemic cells. These data indicate that there is a specific, profound decrease in L-system carrier-mediated amino acid transport in chronic lymphocytic leukemic B cells, as judged by the system-specific synthetic amino acid, 2-amino-2-carboxy-bicyclo (2,2,1)-heptane. This defect was confirmed by studies with two naturally occurring L-system amino acids, leucine and phenylalanine. This specific abnormality of membrane transport by chronic lymphocytic leukemic B lymphocytes is not shared by other B lymphocyte types, and thus appears to be related to the neoplastic nature of the leukemic B cells rather than to their immunologic subtype.

Amino Acids

Neutral carrier electrode for continuous measurement of blood Ca2+ in the extracorporeal circulation.

A neutral-carrier-based Ca2+-selective electrode exposed to whole blood exhibited an EMF-stability better than 0.13 mV (approximately 1% change of the initial activity) during 3.7 to 6.6 h. It has been used successfully to monitor ionic Ca2+ in the extracorporeal circulation during administration of calcitonin to dogs. Data simulation shows that the apparent concentration of ionic Ca2+ is affected by the concentration of Na+. A variation in [Na+] by +/- 5 mmol/L from a value of 143 mmol/L used for the calibration leads to uncertainties of +/- 0.8% in the Ca2+ concentration and +/- 0.2% in the Ca2+ activity if 3 mol/L KCl is used as the reference electrode solution. When an isotonic solution was used as reference electrolyte, errors of +/- 0.8% and +/- 1.7%, respectively, were observed.

Animals

A multicomponent analysis of amino acid transport systems in human lymphocytes. 1. Kinetic parameters of the A and L systems and pathways of uptake of naturally occurring amino acids in blood lymphocytes.

We have determined the kinetic parameters of natural and system-specific synthetic amino acid transport by human blood lymphocytes, using a multi-component computer analysis that separates carrier-mediated uptake from diffusion. These studies were initiated in order to provide the basis for studies of human blood T and B lymphocytes and malignant lymphocytes. Methylaminoisobutyric acid (methyl-AIB) and 2-amino-2-carboxy-bicyclo (2,2,1) heptane (BCH) uptakes into lymphocytes were measured as prototypes of A- and L-system amino acid transport. The Michaelis constant for methyl-AIB uptake was 540 microM; the maximal velocity of uptake was 28 mumol/L cell water/min, and the diffusion coefficient was .004 min-1. In contrast, the Michaelis constant for BCH uptake was 63 microM; the maximal velocity was 969 mumol/L cell water/min, and the diffusion coefficient was .141 min-1. The transport of the naturally occurring amino acids, alanine, proline, and leucine was defined by studies of: (1) competitive inhibition with the system-specific synthetic amino acids, methyl-AIB and BCH, (2) the effect of the transcellular sodium gradient on transport, and (3) evaluation of the time-dependent increase of transport in amino acid-deficient medium (adaptation). Alanine was transported principally (approximately 70%) by the ASC-system, and leucine was transported principally (70%) by the L-system in lymphocytes. The analysis of proline transport was more complex because of a large component of uptake by diffusion even at low amino acid concentrations. Taken together, the kinetics of sodium-sensitive uptake and the results of competitive inhibition studies indicated that proline was transported by the A-system (30%), the ASC system (30%), and also by the L-system (15%).

Amino Acids

Cutaneous ureterostomy as last resort treatment of intractable haemorrhagic cystitis following radiation.

Sixteen patients with severe intractable haemorrhagic cystitis following radiotherapy, two of them with bleeding tumours, were treated surgically by cutaneous ureterostomy with or without contralateral nephrectomy. They had undergone various forms of conservative treatment and were treated by surgery only when conservative therapy had failed. In these poor risk patients a cutaneous ureterostomy was employed as a lesser procedure than an ileal loop. Of the 16 who underwent urinary diversion 11 were completely free of haemorrhage and three continued to have slight intermittent haematuria.

Adult

Potentiometry of Na+ in undiluted serum and urine with use of an improved neutral carrier-based solvent polymeric membrane electrode.

We present an improved Na+-selective liquid membrane electrode for measurement of Na+ concentrations in both undiluted serum and urine. The values for urinary Na+ obtained with the ion-selective electrode agree well with those obtained with the flame photometer. The correlation gives a standard residual deviation of +/- 2.7 mmol/L over the Na+ range of 25-280 mmol/L. In serum, this direct potentiometry yields Na+ concentrations 5.4% (SD 1.1%) higher than those obtained by atomic spectrometry and a standard residual deviation of +/- 1.1 mmol/L. Correction of these values for the volumes of protein and lipid leads to potentiometric values 1.2% (SD 0.7%) lower than those by flame photometry (residual standard deviation: +/- 1.0 mmol/L). Other factors that possibly contribute to this discrepancy are discussed.

Electrodes

Applicability of available ion-selective liquid-membrane microelectrodes to intracellular ion-activity measurements.

The equations that govern the behavior of ion-selective electrodes are evaluated for the composition ranges of Li+, Na+, K+, Mg2+, Ca2+, Cl-, and HCO-3 encountered in living cells. Various cause-effect relations are detailed, especially those pertaining to calibration procedures. The relation of the accuracy of measurement to the expected signal range, particularly in connection with the uncertainty of interpolation, is emphasized. Relevant numerical parameters are given for all ISE's discussed, the selectivity characteristics being those of the most advanced membrane systems. Figures are provided for the calibration curves in the vicinity of the typical cytosol composition.

Animals