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Biomedical subjects

S Thompson

Publications and source records attributed to S Thompson.

At least 289 records · Page 16Linked to original sources

Mapping of antigenic and functional epitopes on the alpha- and beta-subunits of two related mouse glycoproteins involved in cell interactions, LFA-1 and Mac-1.

Mouse Mac-1, a complement receptor-associated surface structure on macrophages, and LFA-1, a function-associated structure on lymphocytes, comprise a novel family of leukocyte differentiation antigens participating in adhesive cell interactions. Mac-1 and LFA-1 contain alpha-subunits of 170,000 and 180,000 Mr, respectively, and beta-subunits of 95,000 Mr noncovalently associated in alpha 1 beta 1 complexes. The structural relation between the alpha- and between the beta-subunits, and the location of functionally important sites on the molecules, have been probed with antibodies. Both non-cross-reactive and cross-reactive monoclonal antibodies (MAb) and antisera prepared to the purified molecules or the LFA-1 alpha-subunits were used. Reactivity with individual subunits was studied by immunoprecipitation after dissociation induced by high pH treatment, or by immunoblotting after SDS-PAGE. Cross-reactive epitopes on Mac-1 and LFA-1 were found to be present on the beta-subunits, which were immunologically identical. Non-cross-reactive epitopes that are distinctive for Mac-1 or LFA-1 were localized to the alpha-subunits. MAb to LFA-1 alpha-subunit epitopes inhibited CTL-mediated killing. Two MAb to Mac-1 alpha-subunit epitopes but not a third MAb to a spatially distinct alpha-epitope inhibited complement receptor function. Neither function was inhibited by a MAb binding to a common beta-subunit epitope. Therefore, sites of Mac-1 and LFA-1 involved in their respective adhesion-related functions, as well as distinctive structural features, have been localized to the alpha-subunits.

Animals↗

Assessment of ventricular size and function in congenitally corrected transposition of the great arteries.

Twenty-four quantitative cineangiographic studies were performed in 19 patients with congenitally corrected transposition of the great arteries to assess right and left ventricular size and function. Ages ranged from 7 days to 44 years and associated lesions included ventricular septal defect (13 of 19), pulmonary stenosis (9 of 19), and systemic (tricuspid) valvular insufficiency (7 of 19). Systemic (anatomically right) ventricular end-diastolic volume was within normal limits in most patients and averaged 119% of predicted normal. Pulmonary (anatomically left) ventricular end-diastolic volume also was normal in most patients, averaged 112% of predicted, and was not different from systemic (right) ventricular end-diastolic volume. Systemic ventricular ejection fraction (RVEF) averaged 0.61 +/- 0.02 and was not different from pulmonary ventricular ejection fraction (LVEF) (0.65 +/- 0.02), but important differences were apparent when age was considered. With exclusion of 2 patients with hypoplastic systemic ventricles and 2 studies performed less than 6 months after open heart surgery, all 12 patients aged less than 10 years had a normal RVEF, whereas 2 of 5 patients aged greater than 17 years had a definitely low RVEF and 1 of 5 had a value at the lower limit of normal. In children, systemic and pulmonary ventricular pump function is usually normal in congenitally corrected transposition of the great arteries and any deviation from normal should suggest ventricular hypoplasia or an increase in afterload. After childhood, systemic ventricular dysfunction is more common and may reflect the inability of the anatomic right ventricle to function as the systemic pumping chamber over a normal lifetime in most patients with congenitally corrected transposition of the great arteries.

Adolescent↗

The nucleotide sequence of the first externally suppressible--1 frameshift mutant, and of some nearby leaky frameshift mutants.

Nine mutants within a 23 nucleotide sequence of the trpE gene of Salmonella typhimurium have been characterized. trpE91, a mutant which is externally suppressible has a single base deletion. Eight (or nine) nucleotides upstream of this deletion, two independently isolated mutations have the same transversion. In combination with trpE91 these mutations lead to partial restoration of synthesis of anthranilate synthetase in the absence of external suppressors. In the transversion the sequence A CA is changed to A AA and this new sequence may be the site where frameshifting occurs to allow leakiness. Leakiness is displayed by two further mutants of the same sign as trpE91, and one of the opposite sign, in the absence of any base substitution or external suppressors. Specific sequences, e.g., UUUC, may be especially prone to frameshifting and this sequence is created at the site of the +1 frameshift mutant which displays leakiness. In the new reading frame generated by the two -1 frame leaky mutants, a tryptophan codon is encountered. Leakiness is necessarily detected in the absence of tryptophan and under these conditions there will be a shortage of charged tryptophan tRNA. The possibility of such functional imbalance leading to frameshifting in these mutants is discussed.

Amino Acid Sequence↗

Spontaneous action potentials and resting potential shifts in fertilized eggs of the tunicate Clavelina.

Electrical activity in the fertilized egg of the tunicate Clavelina was studied with microelectrode recording and voltage clamp techniques. The resting potential could assume either of two stable values (approximately -70 or -30 mV) and could be shifted between these values by direct current stimulation. Spontaneous shifts between two stable resting potentials were also seen. Egg cells produced action potentials spontaneously and in response to depolarizing stimuli. Inward currents were carried by both Na and Ca ions and a prominent outward potassium current was seen with depolarization to voltages above -15 mV. The steady-state current-voltage relationship (I-V curve) of the membrane showed two voltages where the net membrane current equaled zero: approximately -35 and -70 mV. Between these two voltages, membrane current was inward and carried by noninactivating Na and Ca currents. Inward rectification, which was blocked by external Rb, occurred at voltages below -70 mV. The voltage dependence of inward rectification is thought by the authors to be important for establishing the more negative resting potential; it is also thought the presence of inward current which does not inactivate completely at voltages more negative than about -20 mV is an important determinant of the more depolarized resting potential.

Action Potentials↗

Experience with an elimination diet in children with atopic dermatitis.

In order to define possible food-provoking factors, we placed twenty-nine children with chronic atopic dermatitis on an elimination diet. The children remained on their normal diet for 2 weeks followed by 2 weeks on the elimination diet. Foods were then re-introduced at the rate of a new one every 2 days in an attempt to identify foods exacerbating eczema. Thirteen children (45%) completed the elimination diet and seven of these were improved on parental assessment of sleeplessness, itchiness and area of eczema. Five were improved on the dermatologist's assessment. Only two children were able to identify foods provoking their eczema. Sixteen children (55%) failed to complete the elimination diet. Eight felt it was too strict, while eight did not return for follow-up. From our experience, dietary manipulation in older children with chronic atopic dermatitis offers only limited long-term therapeutic gains.

Adolescent↗

Newborn home visits.

A randomized controlled trial was conducted comparing home visits with office visits by physicians to families with newborns within the first two weeks of life. Results showed that physicians were significantly more satisfied and rated their relationship with the family significantly higher after home visits than after office visits. Fathers were present at 50 percent of the home visits compared with 26 percent of office visits (P less than .05). Mothers in the home visit group rated caring for their baby as significantly easier than the office visit group. There was no difference in infant immunization rate or number of well-child visits, although infants in the home visit group had significantly more visits to their own physician. The mean length of visit was 33 minutes (not including travel time) for home visits and 23 minutes for office visits. Physicians were better able to note home environment and family interactions during home visits. This study supports the view that home visits by physicians enhance the physician-family relationship.

Clinical Trials as Topic↗

Retrograde cardiovascular angiography in infants, using a 3.6 French catheter.

Diagnostic retrograde arterial catheterization in infants, and small children has been constrained by the risk of arterial thrombosis and the low flow rate of catheters less than #5 French. We performed retrograde arterial catheterization (percutaneous technique in 21 of 24 patients) on 24 infants and small children (median age 3 months, median weight 4.1 kg), using a 3.6 French performed polyethylene catheter. Systemic heparinization was used. Among the group, we performed 23 aortograms, and 4 selective injections into a bronchial artery; all angiograms were of diagnostic quality. Injection rates ranged from 3 cc/sec to 10 cc/sec (median 5 cc/sec) with a peak developed pressure of 300 PSI to 900 PSI (median 700 PSI). No catheter-related complications were encountered during the study. Four of 24 patients developed a decreased pulse, noted immediately following the catheterization; however, pulses returned to normal within 24 hours, and late blood pressure assessment revealed no abnormalities in the catheterized leg. We now recommend this catheter for infants less than 10 kg when the following angiograms are required: 1. retrograde aortography (truncus arteriosus, pulmonary atresia, aortic stenosis, coarctation, coronary anomalies) 2. selective injections of bronchial arteries 3. retrograde catheterization of surgical shunts.

Angiography↗

Aminopyridine block of transient potassium current.

The blocking action of 4-aminopyridine (4-AP) and 3, 4-diaminopyridine (Di-AP) on transient potassium current (IA) in molluscan central neurons was studied in internal perfusion voltage-clamp experiments. Identical blocking effects were seen when the drugs were applied either externally or internally. It was found that aminopyridines have two kinds of effects on IA channels. The first involves block of open channels during depolarizing pulses and results in a shortening of the time to peak current and an increase in the initial rate of decay of current. This effect of the drug is similar to the block of delayed potassium current by tetraethylammonium (TEA). The other effect is a steady block that increases in strength during hyperpolarization, is removed by depolarization, and is dependent on the frequency of stimulation. The voltage dependence of steady state block approximates the voltage dependence of inactivation gating a changes e-fold in approximately 10 mV. These data suggest that the strength of block may depend on the state of IA gating such that the resting state of the channel with open inactivation gate is more susceptible to block than are the open or inactivated states. A multistate sequential model for IA gating and voltage-dependent AP block is developed.

4-Aminopyridine↗

The abnormal phosphorylation of spectrin in human hereditary spherocytosis.

The phosphorylation of the proteins of the erythrocyte membrane of patients suffering from hereditary spherocytosis is investigated in intact erythrocytes by their incubation in the presence of radioactive inorganic phosphate. Examination of the phosphorylated components by high-resolution two-dimensional gel electrophoresis reveals only one defect in the pathological membranes, a depressed phosphorylation of the smaller polypeptide of spectrin; band 2. The phosphorylation of band 2 is measured with reference to the phosphorylation of syndein (2.1 + 2.2 + 2.3). In patients showing overt clinical symptoms and for whom splenectomy is advocated the phosphorylation of band 2 is depressed by approx. 70%. After splenectomy the phosphorylation of membrane proteins is restored to normal levels.

Adolescent↗

The molecular basis of the defect in phosphorylation of spectrin in human hereditary spherocytosis.

The molecular basis for the depressed phosphorylation of the smaller polypeptide of spectrin (band 2) in the erythrocytes of patients suffering from hereditary spherocytosis is investigated. Comparison of healthy and spherocytic spectrin polypeptides by controlled proteolysis reveals no abnormality in the degradation pattern or in the sites of phosphorylation. It is concluded that the lesion is a consequence of a defective control of phosphorylation. The defect can be mimicked in healthy cells by the introduction of calcium into the erythrocyte and the possibility that the primary pathological lesion is a deficient control of the calcium content of the erythrocyte is discussed.

Adult↗

State of water and electrolytes in mammalian cells during maturation and differentiation.

The state of water and electrolytes was examined 1) in the rat erythroblastic leukemic cell, as a model of a maturing erythrocyte; 2) in the mouse Ehrlich ascites tumor cell during the cell cycle as a model of the uninhibited proliferating cell; and 3) in a clonal population of proliferating and differentiating precursor cells cultured from the bone marrow of the rat. Methods used were phenomenological and included assessments of the volumes of osmotically active water, content of K+, Na+, and Cl-, volumes of distribution for Na+, urea, and ethylene glycol, and the thermodynamics of transport of water and solutes into and out of the cell. The erythroblastic leukemic cell provided evidence for compartments of osmotically active and inactive water and solute. The synchronized ascites tumor cell indicated that these compartments varied during the cell cycle. Membrane function as defined by its permeability to water also varied during the cell cycle. When proliferating cells matured, changes in membrane permeability to water and to nonelectrolytes also correlated with successive stages of differentiation.

Animals↗