The uptake of amines by human erythrocytes in vitro

1. Human erythrocytes incubated at 37 degrees C in Krebs bicarbonate solution at pH 7.5 took up 5-hydroxytryptamine, histamine and (-)-noradrenaline at slow rates which were proportional to the concentration of the amines in the medium at least up to 16 mug/ml., in accordance with a simple diffusion process.2. The initial velocity of uptake was greatest for 5-hydroxytryptamine, about 4 times less for histamine and about 20 times less for (-)-noradrenaline; (+)-noradrenaline was not taken up.3. Comparison of uptake measurements by bio-assay and by radioactivity indicated that, after 1 hr, about 10% of each amine taken up had been inactivated.4. At 2 degrees C the uptake of all three amines was greatly diminished. The presence of the antagonists cocaine, chlorpromazine, lysergic acid diethylamide, mepyramine and pronethalol (at 10(-6) or 10(-5) g/ml.) did not affect uptake of the amines.5. In the steady state the ratios of concentration of the amines between cells and medium were greater than could be accounted for by a Donnan distribution.6. Cells which had taken up amines lost most but not all of them into amine-free medium, at rates which were slower than the corresponding rates of uptake. It was concluded that the amines are partially bound in the cells, noradrenaline most and histamine least.7. The slow diffusion of amines into, and the small amounts retained by, erythrocytes indicate that they do not contribute significantly to the rapid termination of the pharmacological actions of these amines in vivo.     

The Association of Respiratory Infection, Recurrent Hematuria, and Focal Glomerulonephritis with Activation of the Complement System in the Cold

The study of the activation of C3, C5, and C7 associated with the conversion of C3 in the serum of a 9-yr old girl after incubation at 0 degrees C for 6-8 h without utilization of C1, C4, and C2 is described. The patient has upper respiratory infections associated with recurrent gross hematuria, focal glomerulonephritis, and transient renal insufficiency. Histological lesions demonstrated the presence of B1c globulin IgA and properdin in the glomeruli. The activation of complement (C) in the cold requires the patient's IgA. Removal of IgA from the serum by immunoadsorption prevents activation and conversion of C3. Bactericidal and phagocytic activity is also impaired after incubation. C3 proactivator (C3PA) level is reduced before and after incubation. Properdin level drops after incubation. These findings suggest that the activation of C3 which is demonstrable in vitro may be a continuous process in vivo.     

Hospitalization of medicaid children: analysis of small area variations in admission rates.

Population-based hospitalization rates were computed and analyzed for AFDC children among 14 small area subdivisions of the State of Washington. Medical-surgical admission rates ranged from 65.3 to 161.7 per 1,000 person-years among the 14 areas. Surgical admission rates were significantly higher in urban areas; medical admission rates were significantly higher in rural areas. The majority of variance in overall rates was accounted for by admissions for four diagnostic categories: gastroenteritis (18-fold differences), lower respiratory infections (15-fold differences), upper respiratory infections (8-fold differences), and ear, nose, and throat (ENT) surgery (6-fold differences). Secondary analysis indicates that these differences in admission rates were not associated with: medical need or demographic factors, epidemic patterns of disease, physician supply, hospital bed supply or occupancy rates, or severity of disease or delay in seeking medical care as reflected by average length of stay. It is possible that the observed variations may reflect either differences in the propensity of local physicians to hospitalize or differences in the use or adequacy of community, ambulatory, and preventive care.     

CELL KINETIC STUDIES IN MIXED LEUKOCYTE CULTURES: AN in vitro MODEL OF HOMOGRAFT REACTIVITY

The recognition phase of homograft immunity can be studied in vitro in the mixed leukocyte culture reaction. In this reaction, at the end of seven days, up to 30 per cent of the lymphocytes in culture "respond" to a single allogeneic cell stimulus. This paper presents evidence that the lymphocytes responding in culture divide with the generation time of 18-21 hours, with some asynchrony, and that a large percentage of the cells found at the end of the culture period may be the products by division of a small number of cells initially responding. Two estimates are made of the frequency of the initially responding unit (the cell(s) responsible for initiating the response). These are probably minimum estimates and are in the range of 1 in 200 to 1 in 2000 cells which can initially respond. This very high frequency of responding units as compared with the responding units in immediate type hypersensitivity (antibody production) is discussed.     

Benefits provided by an integrated education and clinical diabetes centre: a follow-up study.

The effects of a new integrated system of diabetes care with an enhanced role of the diabetes specialist nurse based in a purposed design diabetes centre, on diabetes control, attendance and cancellation rates, and admission for diabetic emergencies have been reviewed. Glycaemic control was examined in: (a) a cohort of 163 insulin-treated and 47 non-insulin treated diabetic subjects (age < 65 years) studied prospectively before and 3 years following the introduction of a new system of care; (b) a second cohort of more elderly patients aged greater than 65 years studied for the 3 years after the change over; (c) a cross-sectional study of the clinic population (n = 700) the year before and 3 years after the changeover; (d) a group of patients attending standard unaltered clinics in the same district (n = 157). Significant and sustained falls in HbA1 were observed in all groups of subjects attending the centre, with the means for those aged less than 65 falling from 11.9 +/- 2.3% to 9.9 +/- 1.9% and for those aged over 65 from a mean of 11.7 +/- 2.0% to 10.3 +/- 2.3%, 3 years later. The cross-sectional study provided similar results with a mean HbA1 of 12.2 +/- 3.0% prior to changeover and 10.4 +/- 4.4%, 3 years later. Smaller but significant changes were observed in patients continuing to attend the routine clinic (from 12.2 +/- 2.3% to 11.3 +/- 2.6%) over a similar period. Yearly admission rates for ketoacidosis and hypoglycaemia fell from 44 and 23, to 33 and 5 per annum, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypertriglyceridaemia in subjects with normal and abnormal glucose tolerance: relative contributions of insulin secretion,insulin resistance and suppression of plasma non-esterified fatty acids

Summary Although plasma insulin and triglyceride concentrations are positively correlated in many studies, the relationships between insulin resistance, insulin secretion and hypertriglyceridaemia remain unclear. To study these associations, subjects between the ages of 40 and 64 were randomly selected from a general practice register and invited to attend for a standard oral glucose tolerance test for measurement of insulin, triglyceride and non-esterified fatty acid concentrations. The study comprised 1122 subjects who were not previously known to have diabetes and who completed the test. Using the World Health Organisation criteria, 51 subjects were classified to have non-insulin-dependent diabetes mellitus, 188 had impaired glucose tolerance and 883 subjects had normal glucose tolerance. Triglyceride concentrations in subjects with glucose intolerance were elevated compared to those in control subjects, even after adjustment for age, obesity and gender (p<0.001 for subjects with diabetes and p<0.01 for those with impaired glucose tolerance compared to normal subjects). In separate multiple regression analyses for males and females, the most important determinants of the plasma triglyceride concentration were the area under the non-esterified fatty acid suppression curve (p<0.001 in both genders) and the waist-hip ratio (p<0.001 for men and <0.01 for women). The fasting insulin concentration was independently associated with triglyceride concentration in women only (p<0.01). The most important determinant of the area under the non-esterified fatty acid suppression curve in men was the 30-min insulin increment, a measure of insulin secretion, (p<0.001) whereas for women age (p<0.001) and the body mass index (p<0.01) were the most important.Abbreviations NIDDM non-insulin-dependent diabetes mellitus - IGT impaired glucose tolerance - NEFA non-esterified fatty acid