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Biomedical subjects

L R Solomon

Publications and source records attributed to L R Solomon.

At least 55 records · Page 3Linked to original sources

Androgen therapy in haemodialysis patients. II. Effects on red cell metabolism.

Activities of the red cell enzymes hexokinase, glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, lactic dehydrogenase and aspartate aminotransferase were measured in 17 chronic haemodialysis patients receiving androgen therapy, 15 untreated chronic haemodialysis patients and 15 normal subjects. Compared to normal subjects, untreated haemodialysis patients had similar reticulocyte counts but significantly increased levels of all five enzymes studied. This finding suggests the presence of a younger red cell population in the peripheral blood and is consistent with the shortened red cell survival known to occur in this clinical setting. Red cell enzyme activities in untreated haemodialysis patients were significantly correlated with one another and with the serum phosphate level. Moreover, in this population, red cell DPG content was directly related to hexokinase and glucose 6-phosphate dehydrogenase activities while haemoglobin-oxygen affinity (P50) was inversely related to all five enzyme activities. In contrast, in androgen-treated haemodialysis patients, despite higher reticulocyte counts, red cell enzyme activities were the same or lower than those in the untreated haemodialysis group and only slightly higher than those in normal subjects, suggesting an overall older red cell population. Moreover, relationships of red cell enzymes to one another, to serum phosphate levels and to both red cell DPG content and haemoglobin-oxygen affinity were significantly different in androgen-treated subjects than in the untreated haemodialysis group. These changes are consistent with a direct effect of androgens on red cell metabolism and an improved red cell survival during androgen therapy.

2,3-Diphosphoglycerate↗

Methylprednisolone in patients with membranous nephropathy and declining renal function.

Fifteen consecutive patients aged 24 to 70 years, with membranous nephropathy and a progressive decline in renal function, were treated with methylprednisolone, 1 g intravenously daily for five days, followed immediately by a tapering dose of oral prednisolone. Plasma creatinine levels fell by a mean of 46 per cent (range 21-65). In 10 patients the beneficial effect was sustained, but in three it had reversed by six months. In the other two patients the progressive decline of renal function was not influenced. These observations suggest that many patients with membranous nephropathy and declining renal function could benefit from intervention with high dose steroids.

Adult↗

Effect of posture on plasma immunoreactive atrial natriuretic peptide concentrations in man.

The effect of changes of posture on plasma atrial natriuretic peptide concentrations and renal function was studied in normal human volunteers. Plasma atrial natriuretic peptide concentrations increased in the supine posture, reached a maximum value after 30-60 min, remained elevated for 4 h and decreased to baseline values on return to the upright posture. Inflation of antishock trousers, which apply positive pressure to the legs and lower abdomen, attenuated the fall in plasma atrial natriuretic peptide concentration in the upright position. In the supine posture there were increases in urine flow rate, sodium, lithium, fractional sodium and fractional lithium clearances. Fractional distal water and sodium excretion, and total distal water and sodium reabsorption, which were estimated by the lithium clearance technique, also increased. Heart rate and systolic and diastolic blood pressures decreased in the supine and increased on return to the upright posture. Inflation of antishock trousers prevented the increase in heart rate in the upright posture. The contribution of haemodynamic factors to the increase in plasma atrial natriuretic peptide concentrations in the supine position and the relationship between this increase and the associated changes in renal function are discussed. However, the contribution of atrial natriuretic peptide to these changes is uncertain.

Adult↗

Correct NH2-terminal processing of cardiac muscle alpha-isoactin (class II) in a nonmuscle mouse cell.

Both mammalian nonmuscle and muscle actins possess an AcAsp(Glu)NH2 terminus. The nonmuscle actin genes code for a polypeptide with a Met-Asp NH2 terminus (class I) whereas the muscle actin genes code for a polypeptide with a Met-Cys-Asp NH2 terminus (class II). Two amino acids must be removed for mature muscle actin synthesis, whereas only the Met must be removed for nonmuscle actin synthesis. We wished to know whether a nonmuscle cell which normally does not synthesize a class I actin can correctly process a muscle actin with its extra NH2-terminal amino acid in vivo. To answer this question we have used L/LK165 cells, a mouse L-cell transfected with a human cardiac muscle actin gene. When these cells were labeled overnight with [35S]Cys, an actin with an NH2-terminal tryptic peptide corresponding to that of mature cardiac muscle actin was detected. When the cells were pulse-labeled for 20 min, a new actin intermediate containing an AcCys-Asp amino terminus was observed which then disappeared with time. Furthermore, the muscle actin was processed as fast if not faster than the nonmuscle actin in these cells. This actin intermediate was also seen in chick myotube cultures. Our results show that the ability to correctly process muscle specific actins is not tissue specific. Furthermore, these results confirm a processing pathway for class II actins proposed by us earlier on the basis of experiments with a cell-free translation system.

Actins↗

Reticulo-endothelial function in glomerulonephritis.

IgG- and C3b-coated erythrocytes were used to investigate splenic Fc-receptor function and hepatic C3b-receptor function by measurements of their blood clearance. Most patients with glomerular disease including those who were HLA, A1, B8, DR3 had normal Fc-receptor function. Occasional individuals with persistent glomerulonephritis had delayed clearance unrelated to disease activity. In rapidly progressive glomerulonephritis, the phenomenon of 'reticulo-endothelial blockade' was confirmed. C3b-receptor function was normal in most patients with persistent glomerulonephritis. A defect in splenic Fc-receptor function hepatic C3b-receptor function is unlikely to underlie persistent glomerulonephritis.

Adult↗

Bartter's syndrome--observations on the pathophysiology.

The pathophysiology of Bartter's syndrome affecting seven adults has been investigated. (1) Saralasin infusion caused a fall in blood pressure in all patients, suggesting that angiotensin was contributing to the maintenance of blood pressure. (2) Following a water load, urinary chloride concentrations and osmolality were both low. No positive evidence for a defect in chloride reabsorption in the ascending limb of the loop of Henle was obtained. (3) The effect of high and low dietary sodium on plasma sodium, potassium, chloride, magnesium, renin activity, aldosterone, 6-keto-PGF1a, thromboxane B2, urinary kallikrein, platelet function and erythrocyte membrane cation transport were studied. A variety of responses was observed. Sodium restriction increased (or sodium loading decreased), plasma renin activity, aldosterone, 6-keto-PGF1a, urinary kallikrein and the platelet aggregation abnormality in some, but not all, individuals. (4) Treatment with indomethacin was undertaken in all patients and studied in detail in one patient. There was weight gain, increase in plasma sodium and potassium, decrease in capillary pH, positive sodium and potassium balance, and decrease in plasma renin activity, 6-keto-PGF1a, thromboxane B2 and urinary kallikrein. Hypomagnesaemia and excessive urinary magnesium loss persisted unchanged. (5) A variety of abnormalities of erythrocyte membrane cation transport was found and these persisted during high- and low-sodium, and high-potassium intakes; and during treatment with indomethacin, despite correction of intracellular sodium and potassium concentrations. Bartter's syndrome is associated with an abnormality of erythrocyte membrane sodium and potassium transport. Many of the other metabolic abnormalities may be the consequence of potassium and sodium depletion.

Adult↗

Serum ferritin in refractory anemias.

The relationship between the level of erythropoiesis and iron balance was evaluated in 13 subjects with idiopathic refractory anemias. Serum ferritin levels and bone marrow iron stores were increased only in those patients with ring sideroblasts, erythroid hyperplasia and ineffective erythropoiesis. The magnitude of the increase correlated with the duration of anemia and the degree of increase in the erythron iron turnover. Ferritin levels were not related to the severity of the anemia, indicating that increased iron stores did not represent a shift of iron from the erythron or an absorption response to anemia per se. It does suggest that the level of erythroid proliferation directly affects gastrointestinal iron absorption, which in time leads to iron overload.

Adult↗

Reduction of post-transplant proteinuria due to recurrent mesangial proliferative (IgM) glomerulonephritis following plasma exchange.

A patient developed recurrent IgM proliferative glomerulonephritis and a nephrotic syndrome following HLA-identical living donor renal transplantation. Two intensive five-day courses of plasma exchange were followed by sustained reduction of proteinuria. Renal function has remained normal at all times. Immune complex sizing revealed a high titer of middle range complexes (mol. wt. 1 x 10(6) daltons app.); immune complex clearance following an antigen load was not improved by plasma exchange suggesting no alteration of reticulo-endothelial function. Possible mechanisms of benefit are discussed.

Adolescent↗