Estimation of metabolic flux rates in liver purine catabolism of tumour-bearing mice by computer simulation of radioactive tracer experiments.

Mouse hepatocytes from healthy control mice and from Ehrlich ascites tumour-bearing mice were used for tracer-kinetic studies of purine catabolism of liver cells during different periods of tumour growth. The dynamics of the radioactive tracers were modelled mathematically by a system of differential equations. Computer simulations, i.e. direct fitting of numerical solutions of these equations to the observed time-courses of metabolites and specific radioactivities, enables one to estimate unknown kinetic parameters of a simplified model of pathways of hepatic purine catabolism in tumour-bearing mice. There occurred great differences of metabolic flux rates between control hepatocytes, hepatocytes of mice during the proliferating period of tumour growth (6th day after inoculation of the tumour) and hepatocytes of mice during the resting period of tumour growth (12th day after inoculation of the tumour). The final purine degradation of hepatocytes prepared during the proliferating period was lower in comparison with that of control hepatocytes, but it was markedly higher in hepatocytes prepared during the resting period of tumour growth. The changes in hepatocyte purine catabolism during the proliferating period of tumour growth argue for transitions which aim at the maintenance of high purine nucleotide levels in the liver itself rather than for an increased nucleoside and nucleobase supply for the tumour. This suggestion is in accordance with the increased ATP level of the liver during the proliferating phase of tumour growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Platelet Survival in Healthy Volunteers After Storage with N-(2-mercaptopropionyl)-glycine.

The sulphhydryl group containing drug N-(2-mercaptopropionyl)-glycine (MPG) was tested as a cytoprotective substance for storage of human platelets for transfusion. Autologous platelets stored for 48 h at 21 ± 1°C in the absence (control-platelets) or in the presence (MPG-platelets) of MPG, respectively, were labelled with Indium-III oxine and retransfused into the healthy donors. Significantly higher survival and a higher spleen/liver-ratio were obtained using stored MPG-platelets compared to stored control-platelets. Additionally, a very strong correlation was found between the percentage of discocytes counted after incubation of stored platelets in fresh plasma in vitro and the survival of stored platelets after retransfusion in vivo.

Elevated 1,25-dihydroxyvitamin D serum concentrations in infants with subcutaneous fat necrosis.

Two infants with subcutaneous fat necrosis had hypercalcemia that normalized during glucocorticoid treatment. The combination of hypercalcemia, normal concentration of 25-hydroxyvitamin D, an elevated concentration of 1,25-dihydroxyvitamin D, a suppressed parathyroid hormone level, and low-normal bone turnover indicated abnormal 1,25-dihydroxyvitamin D production with increased intestinal absorption of calcium. Unregulated production of 1,25-dihydroxyvitamin D by the granulomatous cells of fat necrosis may cause hypercalcemia.

[Technical orthopedic compensation of leg length inequality]. / Orthopädietechnischer Beinlängenausgleich.

The objectives and limitations in the prescription and construction of leg length adjustments are reviewed. The functional and structural significance of differences in leg length for patients and for healthy persons in different age groups and in different growth phases is considered. A few unconventional ideas, and some information and personal and environmental characteristics are described, leading to a discussion of care criteria that go further than the more usual care systems. It is stressed that interdisciplinary care makes it absolutely essential to note what system of measurement is being used when the treatment is prescribed. Attention is drawn to the possibility of using electrophysiological measurements--whether in the doctor's or physiotherapist's practice or in the orthopedic workshop--for monitoring. Unchanged biomechanical and orthopedic positions are shown in sketches.

Adenine metabolism of Ehrlich mouse ascites cells in proliferating and resting phase of tumor growth.

The incorporation of 14C from [U-14C]adenine into the pools of purine nucleotides, nucleosides and bases in Ehrlich mouse ascites cells (EMAC1) during the proliferating and resting phases of tumor growth was compared. In the proliferating phase the total 14C incorporation into purine pools is much faster than in the resting phase. The ATP turnover as well as the purine breakdown to hypoxanthine and uric acid are increased in the proliferating phase. That corresponds to previous findings on higher nucleotide pool sizes and higher ATP yield and ATP-consuming processes in this growth period.

Determination of the ultraviolet absorbance and radioactivity of purine compounds separated by high-performance liquid chromatography. Application to metabolic flux rate analysis.

A double detection system for the determination of adenine metabolism in biological tissues using isocratic ion-pair reversed-phase chromatography is presented. Two isocratic ion-pair separations were used: (i) 10 mM NH4H2PO4, 2 mM tetrabutylammonium phosphate (PIC reagent A) and 18% acetonitrile for the determination of nucleotides and (ii) 50 mM KH2PO4, 1 mM PIC reagent A and 1% acetonitrile for the determination of monophosphorylated nucleotides, nucleosides and nucleobases. The parallel detection of ultraviolet absorbance at 254 nm and the radioactivity of separated purine compounds allows the detection of pool sizes and of the specific radioactivities in tracer kinetic experiments. The high-performance liquid chromatography methods were applied to the determination of flux rates during adenine nucleotide metabolism in suspensions of Ehrlich mouse ascites tumour cells. The pathways of adenine metabolism in cells during the proliferation and plateau phases of tumour growth were compared.

[Studies on manifestations of Rh-related hemolytic disease of the newborn in the years 1974-1989 in the Erfurt district]. / Untersuchungen über das Auftreten des Rh-bedingten Morbus hämolyticus neonatorum in den Jahren 1974-1989 im Bezirk Erfurt.

In the course of 13 years (1977-1989) 223 of 223,121 liveborn infants in the district of Erfurt suffered from haemolytic disease due to Rh-isoimmunization, 0.1 per cent died. An initial drop of morbidity from 1.6 to 0.6 of 1000 newborns was followed by stagnation and further increase during the last years. More than 50% of the affected babies were delivered by women who had to be protected from sensibilization by immune prophylaxis. The cause for the immunization were deliveries (75%), miscarriages and interruptions (23%). The most important reason for the insufficient decrease of the Rh-morbidity is the failure of immune prophylaxis in the case of ABO-incongruence between mother and child. Our results support the demands for a general immune prophylaxis without taking into consideration the main blood groups and the number and result of the pregnancy. The quantity of severe erythroblastosis (7 stillborn and 5 hydropic liveborn) demonstrates the necessity to improve the prenatal management of these babies.

Antibodies to Epstein-Barr virus-induced early antigens in blood donors.

IgG class antibodies to the early antigen complex (EA; D + R components) of the Epstein-Barr virus (EBV) were found by indirect immunofluorescence in titres greater than or equal to 1:10 in 196 (49.4%) out of 397 blood donors and titres greater than or equal to 1:20 in 84 (21.2%) of these subjects. Anti-EA titres of greater than or equal to 1:2560 were detected in 6 sera, anti-EA(D) only in 17 donors (4.3%). Additional EBV-specific antibody tests were performed in sera with anti-EA-IgG titres of greater than or equal to 1:20 (n = 84), including IgM class antibodies to virus capsid antigen (anti-VCA-IgM). Specific IgM revealed active EBV infection in 12 blood donors. There was no correlation between the presence of anti-VCA-IgM and the magnitude of anti-EA-IgG titres. Therefore, it seems to be impossible to define the threshold titre for EA antibodies indicating active EBV infection. For this purpose probably a titre increase should be demonstrated in paired sera.

[Social structure of the donor sample of a district blood donation and transfusion institute]. / Soziale Struktur des Spenderkollektivs eines Bezirksinstitutes für Blutspende- und Transfusionswesen.

The change from paid blood donation to that made within the Red Cross Organization at the Erfurt District Institute for Blood Donation and Transfusion Service is reflected in the altered composition of the donor population. Team A (n = 4903) consists of "traditional" paid blood donors and Red Cross blood donors. It is characterized as follows: - approximately equal percentage of men and women, - high percentage of working class people with skilled worker's certificate. Women are relatively less frequent among blood donors than men, they are more frequently represented, however, as Red Cross blood donors. Team B (n = 759) covers all new blood donors since 1986, exclusively Red Cross blood donors. It is characterized as follows: - women are represented by 69% (predominantly female students), - the highest percentage (42%) of the team is made up of students. The percentage of blood donors from working class people with a skilled worker's certificate correspond to GDR average. Among the donors graduates from technical colleges and universities are overrepresented, whereas trained working class people with a skilled worker's certificate and those without it are underrepresented. Members of the staff of the municipal health service and Medical Academy as well as students of medicine and education made up the highest percentage of blood donors. About 17% of all members of the medical health service are blood donors, far more than in other branches of Erfurt.

[Lymphocyte function in patients with anti-D(Rh0) antibodies]. / Untersuchungen über die Lymphozytenfunktion bei Personen mit Anti-D(Rh0)-Antikörpern.

The behaviour of humoral and cellular immunity as well as that of cells bearing Fc receptors was investigated in persons with anti-D antibodies. Peripheral lymphocytes could be identified in 6 of 26 examined test persons particularly sensitized against the stroma of Rh-positive erythrocytes. There was no relation to the anti-D titre. The parameters of humoral immunity showed no correlation to the anti-D titre. In 37 per cent of the persons with anti-D antibodies, which were produced "naturally" or artificially, an increased content of IgE could be proved in the serum. In each case, anti-D formation apparently leads to an increase of cells bearing Fc receptors, which can be recognized by the increased number of EA rosettes. A relation to the anti-D titre did not exist. None of the immunological test methods used is suitable for predicting the success of an artificial immunization for the purpose of gaining high titre anti-D antibodies.

[Hepatitis syndrome following heart surgery using extracorporeal circulation]. / Hepatitissyndrome nach Herzoperation mittels Extrakorporalzirkulation.

195 patients who underwent heart operations by means of extra-corporal circulation were followed-up for virus hepatitis in a prospective study. 15 cases of hepatitis occurred, 6 developed hepatitis type B, 9 hepatitis non-A-non-B. 41 out of 142 patients examined had no antibodies against cytomegaly virus, in 7 patients a seroconversion took place. Epstein-Barr-virus does not play a clinical role.

[Genetic factors in anti-D-antibody formation]. / Genetische Faktoren bei der Anti-D-Antikörperbildung.

The blood group specific artificial immunization for producing anti-D-antibodies in Rh-negative persons ("de-novo immunization") is scarcely successful at present and involves risks of health for test persons. With the justified suggestion that the antibody development is genetically influenced even in man, those serological features were being searched for which might reveal a good anti-D-formation, viz. AB0-blood group, HLA antigens and serum groups Hp, Gm and Km. 134 men de-novo immunized were examined. In those persons forming anti-D with a high titre ("high responders") blood group A will be encountered more frequently. Blood group B will frequently occur in "non-responders". In 78 test persons examined in the HLA system was no correlation between the features of the HLA system and the formation of anti-D. The serum features investigated in 71 test persons did not allow any correlation to anti-D formation to be recognized in the Hp, Gm and Km system. It seems reasonable to continue the investigation for relationships between antibody development and certain hereditary characteristics in the human blood, including HLA-DR gene place.

[Hereditary pseudovitamin-D-deficiency rickets with alopecia as a consequence of extreme resistance of target organs to 1.25-(OH)2-cholecalciferol. Therapeutic progress in another disorder of vitamin-D-metabolism (author's transl)]. / Familiäre Pseudovitamin-D-Mangelrachitis mit Alopezie als Folge von hochgradiger Endorganresistenz gegen 1,25-(OH)2-Cholecalciferol. Therapierbarkeit einer weiteren Vitamin-D3-Stoffwechselstörung.

We report about a pair of Turkish siblings suffering from alopecia and severe rickets. In the elder sister we could show the causal role of extreme resistance of target organs to 1.25-(OH)2-cholecalciferol. The birth of a brother who developed the same symptoms together with two other similar cases in siblings recently published by other authors, made it possible to recognize the disorder as a typical syndrome-like entity, based on a hereditary defect. By successful administration of excessive (and so-far not previously published) doses of Vitamin-D3 a way for therapeutic progress in this new type of vitamin-D-dependent rickets is shown.