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Biomedical subjects
Publications and source records attributed to B Lederer.
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Glycerophosphate acyltransferase present in an extract of rat adipocytes is strongly inhibited by excess palmitoyl-CoA. This inhibition is released by serum albumin but an excess of serum albumin is inhibitory, particularly at low palmitoyl-CoA concentrations. An optimal activity is reached when the ratio palmitoyl-CoA/albumin is in the range of 3-6. In the absence of albumin, oleic acid inhibits the activity at all palmitoyl-CoA concentrations. This inhibition is released by albumin and, inversely, oleic acid releases the inhibition by high concentrations of albumin. Another effect of fatty acids is to favour the inactivation of the glycerophosphate acyltransferase in extracts of adipocytes kept at 0 degree C. This inactivation is time-dependent and cannot be reversed by the addition of albumin to the assay mixture. Treatment of adipocytes with noradrenaline had no effect on the activity of the enzyme as long as the cells had been separated from fatty acids and albumin. With extracts of unwashed cells, the effect of noradrenaline on both the activity and stability of glycerophosphate acyltransferase could be explained by the presence of fatty acids in the extract.
We confirmed that, as reported by Sooranna & Saggerson [(1982) Biochem. J. 202, 753-758], the affinity of 6-phosphofructo-1-kinase (PFK) for fructose 6-phosphate in an adipocyte extract was increased after incubation of the cells in the presence of noradrenaline. The participation of fructose 2,6-bisphosphate in this kinetic modification could be excluded, because the noradrenaline effect persisted after extensive gel filtration of the extracts and also because the treatment did not cause any change in the concentration of fructose 2,6-bisphosphate in the adipocytes. Oleic acid was found to be another potent positive effector of PFK in an adipocyte extract, with a Ka of 10 microM. Its effect was synergistic with that of fructose 2,6-bisphosphate and AMP, and was counteracted by serum albumin. Palmitic acid had a similar effect. We conclude that the large increase in fatty acid concentration caused by noradrenaline treatment is an explanation for the activation of phosphofructokinase at low fructose 6-phosphate concentrations in an adipocyte extract.
In this prospective study, primary urothelial bladder tumour specimens from 64 patients were investigated by means of DNA Feulgen cytophotometry. The patients were followed clinically for at least 7 years. The objective cytophotometric parameters correlated well with the histopathological grading and the cytochemical data were of considerable prognostic value. They were closely correlated with the stage of the tumour, 5- and 7-year survival rates and the probability of tumour recurrence. It is concluded that DNA cytophotometry can serve as a method for the standardisation of histological grading and can give more objective and more detailed prognostic information than conventional histopathology.
Successful percutaneous transluminal dilatation of an anonyma stenosis is reported. The patient was a 40 year-old male with the aortic arch syndrome. Five years before an occlusion of the central carotid artery, as well as anonyma and left subclavian stenoses were treated by means of vascular grafts. On recurrence of the neurological symptoms, reocclusion of the right graft to the anonyma artery and subtotal stenosis of the left carotid bifurcation was noted. The anonyma stenosis was dilated by means of PTD. Haemodynamic success was demonstrated by Doppler sonography.
Pyrophosphate : fructose-6-phosphate phosphotransferase (PPi-PFK) has been purified 150-fold from potato tubers and the kinetic properties of the purified enzyme have been investigated both in the forward and the reverse direction. Saturation curves for fructose 6-phosphate and also for fructose 1,6-bisphosphate were sigmoidal whereas those for PPi and Pi were hyperbolic. In the presence of fructose 2,6-bisphosphate, the affinity for fructose 6-phosphate and for fructose 1,6-bisphosphate were greatly increased and the kinetics became Michaëlian. The effect of fructose 2,6-bisphosphate was increased by the presence of fructose 6-phosphate and decreased by the presence of Pi. Consequently, the Ka for fructose 2,6-bisphosphate was as low as 5 nM for the forward reaction and reached 150 nM for the reverse reaction. On the basis of these properties, a procedure allowing one to measure fructose 2,6-bisphosphate in amounts lower than a picomole, is described.
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A girl presented with an important growth retardation, hepatomegaly, fasting hypoglycemia, lactic acidosis, increased serum cholesterol, triglycerides and uric acid, and increased liver glycogen (7.5%). There was no rise in blood glucose after IV galactose or fructose, but glucagon gave a delayed response. Type Ib glycogen storage disease was suggested by the low normal activity of glucose-6-phosphatase (G-6-Pase) which reached 1.8 units/g (normal, 2 to 10 units/g) and the normal activity of other glycogenolytic enzymes, measured in homogenates prepared in H2O (mean +/- S.E. in control subjects: 59% +/- 7; in type Ia GSD: 92% +/- 3). The activity of G-6-Pase measured as described above increased to 3.8 units/g of liver 1 year after PCS and 7.85 units/g of liver after 3 years. At that time, a simultaneous assay of the enzyme in a fresh, previously not frozen liver biopsy, homogenized in 0.25 M sucrose, revealed only about 29% of the activity of the same sample prepared in H2O (mean +/- S.E. in three controls: 95.8% +/- 8.9.
Amniocentesis was performed 56 times in 42 pregnant women with Rh immunisation. In 6 cases of Rh immunisation there was a high delta bilirubin extinction in the B zone of the Liley diagram; in these cases immunosuppressive therapy with corticosteroids was applied. In all these cases also exsanguinotransfusion in children proved necessary. In 16 pregnant women, in whom the delta bilirubin extinction was in the A zone of the Liley diagram, high bilirubin values required exsanguinotransfusion in children.
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Forty-nine patients with transitional cell tumors of the urinary bladder were followed up clinically for a period of at least 36 months (average time 61.4 months). Initial tumors were examined by means of DNA-Feulgencytophotometry. Histologic grading was performed according to Bergkvist et al. (1965). Clinical behavior clearly demonstrates the validity of the grading schedule used and shows the significance of DNA-Feulgencytophotometry for the standardization of bladder tumors and for the comparability of diagnostic and therapeutic results. Determination of the individual prognosis of low-malignancy tumors and the differentiation of histologic borderline cases does not appear to be possible by means of DNA-Feulgencytophotometry.
Two patients with symptoms of progressive obstructive jaundice, a history of vague pains in the right upper quadrant and laboratory evidence of biliary obstruction underwent laparotomy. A stone-free, but extremely thick-walled gallbladder was found in both patients. Intraoperative cholangiography showed diffusely-stenosed extrahepatic bile ducts suggestive of chronic inflammatory changes in the biliary system. The correct diagnosis was made only on histological examination, which revealed primary sclerosing cholangitis with secondary cholestatic changes of the liver. Postoperative treatment included long-time corticosteroid therapy. Both patients have remained jaundice-free for periods of one and two years, respectively, to date, but the eventual prognosis is poor. The diagnosis, which can be made only surgically, therapy and prognosis are discussed.
Two cases of the uterine inversion during cord traction is described. Both women were primiparae, aged 26 and 19, respectively. Once there was a shorter umbilical cord and once the adherent placenta. In both cases the manual reposition of the uterus proved successful, but the patients were threatened by the shock, one of them even developed the heart arrest. The authors draw attention to the fact that the cord traction method in the third stage of labour could be exceptionally dangerous, in spite of its other advantages.
Ten patients with normal liver and kidney functions were admitted to a urology department for prostatectomy because of benign prostatic hypertrophy. They received a twice daily administration of 2 tablets of sulfametrole/trimethoprim (Lidaprim) for 4 days; the last dose of 2 tablets was given 4 hours before surgery. Having been enucleated by the suprapubic route, the prostatic glands were examined both histologically and chemico-analytically. The concentrations of the chemotherapeutically active substances were determined in the plasma and in the prostatic tissues. The prostatic tissue concentration of sulfametrole was 24,0 +/- 8,6 mg/kg and that of trimethoprim 7,1 +/- 2,2 mg/kg.
Immunological investigations concerning pathological autoantibodies and defects of humoral immunity were performed in 7 patients with thymomas, 5 of which showed invasive growth. The number of B and T lymphocytes in blood was determined at the same time using membrane markers as well as blood lymphocyte stimulation with phytohaemagglutinine. Two of the 3 patients with auto-antibodies against striated muscles or nuclei showed the clinical signs of accompanying disease (myasthenia gravis, lupus erythematodes). A humoral immunodisturbance with IgM deficiency was demonstrable in one patient and was accompanied by clinical symptoms. Lymphopenia with decreased numbers and functional disturbance of T and B lymphocytes could be shown in the majority of patients. Immunological investigations simplify proof of accompanying diseases in thymomas. These represent an important prognostic criterium in the same way as does invasive growth.
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We suggest to differentiate between the real spontaneous perforation of the gallbladder and the inflammatory rupture and contrast both with the traumatic form. In one case treated by us we suceeded in finding the cause of the perforation to be an antatomical deficiency. Sterile cholascos should be distinguished from severe bile peritonitis.