Promotion of lymphocyte growth by high density lipoproteins (HDL). Physiological significance of the HDL binding site.

The characteristics and physiological relevance of the high density lipoprotein (HDL) binding site on unstimulated and mitogen activated human peripheral blood lymphocytes have been investigated. At 37 degrees C, specific binding/uptake of fluorescent (dioctadecylin-docarbocyanine, DiI) HDL was observed by cells from healthy donors as well as by those from low density lipoprotein receptor-defective patients; mitogen activated T-blasts exhibited a markedly elevated DiI-HDL uptake compared to resting T-cells. Binding was saturable at 37 degrees C and of high affinity, with a Kd of 5 x 10(-8) M. It was blocked by anti-apoAI polyclonal antibodies (F(ab)2 fraction), but not by anti-apolipoprotein (apo)E, anti-apoAII, or anti-apoB, and was inhibited competitively by HDL apoproteins and an apoAI-protein A fusion protein. T-cell associated DiI-HDL was increased by trypsin treatment (of the cells) and decreased by activation in the presence of HDL or low density lipoprotein. Comparison of the concentration dependencies of growth promotion and specific cell association of HDL indicated that two mechanisms of lipid exchange may be in operation: one a binding-dependent mechanism of cholesterol exchange, with maximal effect in the HDL concentration range (20-200 micrograms/ml) in which specific binding increases rapidly, and the other a binding-independent exchange of lipids effective at concentrations in which specific binding is saturated (300-5000 micrograms/ml).

[Seckel dwarfism based on a personal case]. / Uber den Seckel'schen Zwergwuchs anhand einer eigenen Beobachtung.

Report on a girl with Seckel-syndrome (bird-headed dwarfism). In addition to the known symptomatology she had a congenital heart failure (ASD II, VSD, PDA). Endocrine evaluation revealed decreased growth hormone stimulation. In the CT-scan of the skull enlarged ventricles were demonstrated.

[Glucose tolerance test in morbidly obese children and adolescents]. / Glukosetoleranztest bei hochgradig übergewichtigen Kindern und Jugendlichen.

Oral glucose tolerance tests (50 g/m2 body surface) were performed in fifty-two children and adolescents (28 girls and 24 boys) aged 3.1 to 16.8 (mean +/- SD 11.4 +/- 3.28) years. Mean overweight of the patients was calculated to be 69.7 +/- 28.5%. Plasma glucose and immunoreactive insulin were determined before, and 15, 30, 60, 90, 120 and 180 minutes after the oral glucose load. According to the criteria of the National Diabetes Data Group six (11.5%) of the subjects had abnormal glucose test profiles (fasting glucose concentrations over 140 mg/dl or after 120 minutes above 140 mg/dl), and in four of the six probands we could detect elevated fasting insulin levels (above 17 E/ml) as well. In twenty-three out of forty-eight serum samples (47.9%) basal insulin levels were elevated. No correlation between age, sex, duration of overweight with glucose or insulin levels could be found. Our results are in accordance with findings in obese adults reflecting a high prevalence of impaired glucose tolerance and hyperinsulinemia in obese children and adolescents. On the other hand pathophysiologic relevance and clinical importance of these findings in obese children of an impaired glucose tolerance and hyperinsulinemia is questionable in view of the rapid normalization after weight loss.

Usefulness of antistreptolysin titre determination in Still's syndrome.

ASL-titer determination obviously can be used to document successful drug intervention in patients with Still's syndrome.

Ciclosporin monitoring in kidney-transplanted children: high-performance liquid chromatography versus radioimmunoassay.

Due to large individual differences in absorption, utilization and metabolism of the predominantly used drug ciclosporin (CsA) for selective immunosuppression in kidney graft recipients, therapeutic blood levels (immunosuppression/toxicity) can be maintained only by frequent measurements of the CsA concentrations in blood samples and dosage readjustments. The purpose of the present study was to investigate the usefulness of a high-performance liquid chromatography (HPLC) method for native CsA and a radioimmunoassay (RIA) method for CsA and metabolites measuring simultaneously using both HPLC and RIA and creatinine serum levels (Crea) in whole blood samples from 19 kidney-transplanted children over a 3-year observation period. By comparison of the results of HPLC, RIA and Crea determinations (n = 1,284) we found a highly variable metabolization rate (RIA/HPLC ratio) of 5.25 +/- 2.33 (range 1.37-12.9). No direct correlation was found between changes in RIA/HPLC ratios and kidney function, rejection and infection periods. Dosage/HPLC and dosage/RIA showed no significant correlation. A higher correlation between HPLC, Crea and nephrotoxicity was found than between RIA and Crea. Because of rapid and large variations of CsA metabolization rates in young allograft recipients, we recommend measurements of CsA blood concentrations with any HPLC method specific for unchanged drug, since CsA metabolites detected by RIA, at least those which are most abundant, have less immunosuppressive and toxic effects.

Neopterin and interferon gamma serum levels in renal allograft recipients.

In the follow-up of children receiving renal allografts the early differential diagnosis of infections and rejection episodes is the main problem. Serum levels of neopterin (N), a pteridine released from stimulated macrophages, was determined by radioimmunoassay. Also interferon-gamma (IF) serum levels, a marker of T lymphocyte activity, were determined with an immunoradiometric assay in 19 kidney-transplanted children. Both, infections and rejection episodes, are accompanied by distinct increases in N. The IF are elevated 1-3 days earlier than N, the median values during infections being significantly (p less than or equal to 0.001) higher than those during rejection crises. The routine measurement of N and IF allow the simple, quick and reliable monitoring of the immune status, which seems to be of a high relevance for the daily monitoring of transplant recipients.

[Protein malnutrition in pediatric patients with oncologic diseases]. / Protein-Malnutrition bei pädiatrischen Patienten mit onkologischen Erkrankungen.

To study the frequency of protein-caloric malnutrition in children (n = 16) with malignant diseases, we measured serum-albumin, -transferrin, -prealbumin and -retinol-binding protein (Radial immunodiffusion) before treatment was started. In 9 children at least 3 of the 4 rapid-turnover proteins were below the age-specific reference values. 7 patients (44%) with low rapid turnover proteins were free from infection, liver and renal dysfunction and thus, diagnosis of protein-caloric malnutrition was established. Anthropometric parameters as weight for age and the weight/height ratio did not predict protein-caloric malnutrition. Nutritional therapy (enteral, parenteral) during a period of 2 weeks resulted in significant increase of albumin (p less than 0.05), prealbumin (p less than 0.01) and retinol-binding protein (p less than 0.01). Rapid turnover proteins can be easily measured in each laboratory and are useful in diagnosis and treatment of protein-caloric malnutrition of children with malignant diseases as long as the limitations of this method are not neglected.

Chronobiology of urinary acid glycosaminoglycan excretion.

Acid glycosaminoglycans (AGAG, mucopolysaccharides) are major constituents of the extracellular matrix. They play a role in filtration and permeability processes, isolation and scaffolding. In childhood no circadian rhythms have been reported up to now. We examined 11 children testing the parameters of: urine volume, creatinine concentration and -excretion, glycosaminoglycan concentration and -excretion, the glycosaminoglycan/creatinine ratio, chondroitin 4 sulfate (Ch4S) in % of total AGAG, Ch4S in mg/2 hrs, heparan sulfate (HS) in % of total AGAG and HS in mg/2 hrs. The biorhythmicity of these data were processed by the cosinor system. We found significant circadian rhythmus for urine volume (acrophase at 1704 hrs, p = 0.05), creatinine concentration (acrophase at 0512 hrs, p = 0.01) and glycosaminoglycan concentration (acrophase at 0358 hrs, p = 0.005). The data presented can form the physiological basis for studies of biorhythmicity in several pathological states as e.g. diabetes and mucopolysaccaridoses.