Regulation of cAMP in a lymphocyte preparation isolated from peripheral venous blood in human subjects: the significance of residual thrombocytes, noradrenaline and prostaglandins.

1. The aim of the study was to elucidate the mechanism of the previously reported close correlation observed between noradrenaline and cAMP in a lymphocyte preparation (LP) isolated from peripheral venous blood in healthy subjects. A close correlation was also obtained in the present study between lymphocyte noradrenaline and adrenaline and cAMP both in the basal state and after stimulation with isoproterenol (P<0.05 to 0.007).2. Although 99% of the thrombocytes were removed from the LP during the washing procedure, LP contained approximately one thrombocyte per lymphocyte. The noradrenaline concentration in LP which could be ascribed to residual thrombocytes, calculated from the average noradrenaline concentration in thrombocytes and the number of thrombocytes in LP, correlated closely to noradrenaline in LP (P<0.007).3. To test the hypothesis that noradrenaline in LP was primarily derived from plasma, we studied three patients with phaeochromocytoma, who had high levels of noradrenaline and adrenaline both in plasma and in LP. 4. Further studies showed that the addition of thrombocytes to LP increased cAMP. The response was inhibited by indomethacin, whereas the addition of cimetidine and propranolol had no effect on basal or thrombocyte-stimulated cAMP.5.We conclude that noradrenaline in LP is a marker of the number of residual thrombocytes. The addition of thrombocytes to LP increased cAMP in lymphocytes. This response was not mediated by catecholamines but possibly by prostaglandins.

Thyrotropin receptor antibodies and Graves' disease, a side-effect of 131I treatment in patients with nontoxic goiter.

The use of 131I treatment in patients with benign nontoxic goiter is increasing, and the described side-effects are few. In this paper we describe appearance of TSH receptor antibodies (TRAb) and concomitant development of hyperthyroidism as a side-effect of 131I treatment in patients with nontoxic goiter. In this retrospective study, 191 consecutive patients with 131I-treated nontoxic goiter are described. Nine patients (5%) developed hyperthyroidism 3 months after 131I treatment, and 5 patients (3%) developed radiation thyroiditis within the first month. Frozen sera were analyzed for thyroid peroxidase antibodies (anti-TPO) in 130 patients before 131I treatment. In 21% of these, serum levels of anti-TPO were over 200 U/mL. The complication frequency of Graves'-like hyperthyroidism and hypothyroidism was 51% in patients with elevated anti-TPO (n = 27) and 15% in patients with normal serum anti-TPO levels (P < 0.00005). TRAb, anti-TPO, and thyroglobulin were followed in patients developing hyperthyroidism or radiation thyroiditis and in 10 control patients remaining euthyroid. At the time of 131I treatment, all patients had serum TRAb values within the normal range. Three months after administration of 131I, the patients developing hyperthyroidism had a transient extensive rise in serum TRAb and anti-TPO levels parallel to a rise in the serum free T4 index. In patients developing radiation thyroiditis, serum TRAb values were normal. In control patients, serum TRAb and anti-TPO values were both within the normal range throughout the observation period. In conclusion, hyperthyroidism can be triggered by 131I in patients with nontoxic goiter, not only related to radiation thyroiditis but also as a Graves'-like hyperthyroidism induced by TRAb. Elevated anti-TPO pretreatment is a marker of an increased risk of side-effects to 131I treatment in nontoxic goiter.

Lymphocyte norepinephrine and epinephrine as indices of long-term changes in sympathoadrenal activity in human subjects.

NASA: Researchers propose that long-term changes in sympathoadrenal activity during space flight can be evaluated by lymphocyte norepinephrine measurements in the early post-flight period. The metabolism of thrombocyte and lymphocyte catecholamines is explored to support the hypothesis.^ieng

Lymphocyte cAMP and ageing: significance of subset composition, plasma noradrenaline, regular physical training and long-term smoking.

1. We studied 37 healthy men at rest in the supine. position to examine the effect of ageing, smoking and physical training of beta 2-adrenoceptor function, plasma catecholamines and the proportions of various lymphocyte subsets. 2. In 14 young subjects the proportion of natural killer cells was correlated with cAMP production in lymphocytes and inversely correlated with plasma noradrenaline level. 3. In 16 elderly non-smokers plasma noradrenaline was negatively correlated with the natural killer cell subset CD3-CD16+. Lymphocyte cAMP responses did not differ between young and elderly non-smokers, whereas plasma noradrenaline increased slightly but significantly with age. Physical training did not influence either plasma noradrenaline or adrenaline at rest or cAMP in lymphocytes. 4. In seven elderly long-term smokers cAMP production and the viability of lymphocytes were reduced. Plasma noradrenaline attained its highest values in long-term smokers. 5. It is concluded that cAMP production and plasma noradrenaline are related to lymphocyte subset composition. The greater the proportion of natural killer cells and related subsets, the higher is cAMP production and the lower is plasma noradrenaline. Thus, the inverse correlation between lymphocyte cAMP and plasma noradrenaline is indirect and most likely mediated by variability in lymphocyte subset composition. In elderly subjects, reduced cAMP production was observed in long-term smokers, and this abnormality was probably due to a reduced viability of lymphocytes and especially of natural killer cells. The negative correlation between the proportion of natural killer cells and plasma noradrenaline at rest contracts with a well-known mobilizing effect of adrenaline on natural killer cells.

Lymphocyte norepinephrine and epinephrine, but not plasma catecholamines predict lymphocyte cAMP production.

Endogenous norepinephrine (NE) and epinephrine (E) were demonstrated in lymphocytes isolated from peripheral venous blood. In 13 young subjects lymphocyte NE and E averaged 14.3 and 1.9 pg per 10(7) cells, respectively. The ratio NE/E was similar in plasma and in lymphocytes. Highly significant correlations were obtained between lymphocyte NE and E on the one hand and cAMP in lymphocytes on the other both in the basal state and after stimulation with isoproterenol. In a group of elderly subjects lymphocyte NE concentration was significantly reduced in long-term smokers as compared to non-smokers (7 and 35 pg/10(7) cells, respectively), whereas plasma NE was increased in smokers. Addition of exogenous NE or propranolol to blood samples did not change lymphocyte NE concentration in in vitro experiments. Variability in endogenous lymphocyte concentration of E in 9 young subjects, correlated with concomitant changes in number of NK(CD3-CD56+) cells and cAMP. It is concluded that endogenous lymphocyte NE and E concentrations in healthy subjects reflected basal cAMP production in lymphocytes and lymphocyte subset composition.

Lymphocyte subset composition in peripheral blood from normal subjects may be influenced by both spleen size and plasma norepinephrine.

The aim of the present study was twofold: (a) to confirm a previously observed negative relationship between plasma catecholamines and the percentage of natural killer (NK) cells in peripheral blood from resting human subjects, and (b) to examine the relationship between the size of the spleen and the composition of circulating lymphocyte subsets in resting subjects. A total of 14 young healthy male subjects were investigated in a supine resting position. Lymphocyte subset composition was determined with two-colour flow cytometry, and lymphocyte subsets were expressed as percentages of mononuclear cells. Spleen size was evaluated with ultrasonography. Plasma catecholamines were determined. Plasma norepinephrine and the percentage of NK-cells (CD3-CD56+) were negatively correlated (rs = -0.62, p = 0.019). The CD4/CD8 ratio and plasma norepinephrine were positively correlated (rs = 0.57, p = 0.037) and the major part of this correlation was due to a correlation between plasma norepinephrine and the percentage of CD4+ cells. The percentage of NK cells (CD3-CD56+) was predicted by a multiple regression model including the percentage of CD8+ cells and the spleen index, a measure of spleen size (r = 0.93, p < 0.001). The correlation in the resting state between plasma norepinephrine and the percentage of NK cells (negative correlation) on the one hand and the CD4/CD8 ratio (positive correlation) on the other contrasts with the acute mobilizing effects of epinephrine, isoproterenol and exercise on lymphocyte subsets. These relationships remain unexplained, but results accord with the hypothesis that catecholamines may have dual effects on lymphocyte subsets. The results support the view that the spleen may have a depot function for NK cells.

Increased transcapillary escape rate of albumin in elderly subjects due to long-term smoking habits.

Transcapillary escape rate of albumin (TER) expressed as percentage decrease in specific activity of plasma albumin per hour was measured in 44 healthy male subjects, 10 young non-smokers (median age 24.0 years, range 21-33), 10 young smokers (30.5 years, range 27-36), 10 elderly non-smokers (64.0 years, range 51-75) and 14 elderly smokers (61.5 years, range 54-69). In addition urinary albumin excretion rates were measured in 15 of the elderly subjects. The subjects were investigated after overnight fasting and abstention from tobacco. Median TER was 7.33% (interquartile range 5.82-9.90) in the elderly smoking subjects. This value was significantly elevated as compared to elderly non-smokers, 4.47% (2.93-5.83), young non-smokers, 3.70% (2.24-6.30) and young smokers, 4.25% (2.80-4.44). A statistically non-significant (P = 0.064) tendency of a higher urinary albumin excretion rate was observed in elderly smokers. This agrees with other investigations showing slightly increased albuminuria in smokers compared with non-smokers. The differences were not related to differences in blood pressure, plasma cholesterol, weight, or abuse of alcohol in the elderly subjects. Diabetic subjects with an increased TER to levels comparable with levels in long-term smokers have increased urinary albumin excretion rates, which seems to be greater than in long-term smoking subjects. It is suggested that increased TER in long-term smokers may indicate a vascular dysfunction affecting either capillary permeability or endothelial surface area.

Individual lymphocyte subset composition determines cAMP response to isoproterenol in mononuclear cell preparations from peripheral blood.

The aim of the present study was to examine to what extent isoproterenol-stimulated cAMP production in mononuclear cells, isolated from resting human subjects, was correlated with lymphocyte subset composition. Peripheral blood was collected from 14 healthy male subjects, who rested in the sitting position. Mononuclear cells were prepared by density centrifugation and subset composition was determined by two-colour flow cytometry. Cyclic AMP production was determined by a radioimmunoassay after inhibition of phosphodiesterase and stimulation with isoproterenol. NK-cells (CD3-CD56+) were positively correlated to total cAMP concentrations (basal cAMP plus increase in cAMP). Tcytotoxic cells (CD8+) were positively correlated to the relative increase in cAMP. Thelper cells (CD4+) were negatively correlated to total cAMP concentrations and B-lymphocytes (CD(19+20)+) were negatively correlated to the relative increase in cAMP. The results support the view that NK-cells and Tcytotoxic cells have higher beta 2-adrenoceptor densities and more receptors with high affinity than Thelper and B-cells. In conclusion, our study demonstrates that cAMP levels in blood mononuclear cells obtained from normal subjects show substantial variation. This variation is at least in part due to differences in lymphocyte subset composition in the same subjects. Therefore, it is important to know the lymphocyte subset composition when evaluating cAMP accumulation in mononuclear cell preparations from peripheral blood.

Percentage of NK-cells in peripheral blood in resting normal subjects is negatively correlated to plasma adrenaline.

The purpose of the present study was to examine, if there was a correlation between natural killer cells in blood and plasma catecholamines in a resting situation. Lymphocyte subsets, especially, the NK-cells (CD3-CD56+), plasma adrenaline and noradrenaline were determined in peripheral blood from healthy male subjects resting in the supine position. Median age was 32 years. A negative correlation was observed between resting plasma adrenaline and the percentage of (CD3-CD56+) mononuclear cells (p = 0.048, r = -0.61). Previous studies have shown however, that adrenaline may increase the number of natural killer cells in blood within minutes. We suggest that adrenaline may have a dual effect on NK-cells: an acute effect by which NK-cells are mobilized from depots and a chronic effect, which decreases the number of lymphocytes and especially NK-cells in peripheral blood.

[Acute appendicitis and gastrointestinal tuberculosis with negative thoracic X-ray and positive sputum culture]. / Appendicitis acuta og gastrointestinal tuberkulose med negativt røntgen af thorax og positiv ekspektoratdyrkning.

A case of gastrointestinal tuberculosis is presented with negative radiographic findings in the thorax and positive results of culture of the sputum. The value of radiographic examination of the thorax for demonstration of tuberculosis is briefly discussed on the basis of the literature. Normal radiographic findings in the thorax do not exclude gastrointestinal tuberculosis. Radiographic examination of the thorax only reveals active pulmonary tuberculosis in approximately 50% of the patients with gastrointestinal tuberculosis. Pulmonary tuberculosis with positive sputum culture can be demonstrated in up to 50% of the patients with gastrointestinal tuberculosis. Most frequently, demonstration of acid-fast rods or positive culture from biopsy specimens or material obtained at laparotomy cannot be anticipated. Opinions differ as to whether histological evidence of tuberculosis in the form of caseous granulomata occurs frequently in gastrointestinal tuberculosis. The greatest chance of demonstration is to be found in the lymph nodes draining the region concerned. This was the case in the patient presented here where caseous necrosis and epithelioid cell granulomata were demonstrated.